Дисертації з теми "Cutaneous carcinoma"
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Lambert, Sally Ruth. "Molecular profiling of cutaneous squamous cell carcinoma." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/564.
Robinson, Kim. "Identification of novel molecular targets for cutaneous squamous cell carcinoma." Thesis, University of Dundee, 2014. https://discovery.dundee.ac.uk/en/studentTheses/78349252-d233-40ad-9724-7b186baf531b.
Pirzado, Muhammad Suleman. "Investigating cell senescence in basal cell carcinoma." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8633.
Rose, Aidan Michael. "Transforming growth factor-beta signalling in human cutaneous squamous cell carcinoma." Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/51b1a1c1-ac43-4f60-aa77-9002af3f2186.
Dworkin, Amy Marie. "ENVIRONMENTAL AND GENETIC CONTRIBUTIONS OF SUSCEPTIBILITY TO CUTANEOUS SQUAMOUS CELL CARCINOMA." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1266000583.
Ismail, Ferina. "Ultraviolet Radiation-induced Apoptosis in the Pathogenesis of Cutaneous Squamous Cell Carcinoma." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522322.
Azimi, Ali. "PROTEOMIC ANALYSIS OF ACTINIC KERATOSIS, BOWEN’S DISEASE AND CUTANEOUS SQUAMOUS CELL CARCINOMA." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20449.
Emich, Helena. "Clinical implications of cancer stem cell properties in oral squamous cell carcinoma." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8479.
Martins, Vera Lisa Coelho. "Increased invasive behaviour of cutaneous squamous cell carcinoma with knock-down of Type VII collagen." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497913.
Mooney, Craig Paul. "Cutaneous Squamous Cell Carcinoma of the Head and Neck Identifying Metastasis and High-Risk Characteristics." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/24946.
Rahman, Muhammad Mahmudur. "Characterisation of a novel in vitro model of basal cell carcinoma (BCC) through stable PTCH1 suppression in immortalised human keratinocytes." Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8658.
Gressel, Katherine Lynne. "Alterations in Endogenous Retinoids with Acute UVB Exposure and in the Progression of Cutaneous Squamous Cell Carcinoma." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429785553.
Pyczek, Joanna [Verfasser], Heidi [Akademischer Betreuer] Hahn, Michael [Gutachter] Schön, and Holger [Gutachter] Bastians. "Hedgehog signaling in cutaneous squamous cell carcinoma / Joanna Pyczek ; Gutachter: Michael Schön, Holger Bastians ; Betreuer: Heidi Hahn." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2018. http://d-nb.info/1151398918/34.
Ramachandran, Sudarshan. "Identification of genetic and host factors associated with clinical phenotypes in patients with cutaneous basal cell carcinoma." Thesis, Keele University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402689.
Fleming, Jessica L. "Utilizing Cancer Resistant and Susceptible Mice to Identify the Genetic Contributions to Cutaneous Squamous Cell Carcinoma Susceptibility." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1354289625.
Al-Myouf, Abdullah Abdulaziz. "Cadherins, catenins and associated proteins in normal epidermis, basal cell carcinoma and other cutaneous tumours : an immunohistochemical study." Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341723.
Gomaa, Wafaey Mohammad. "Role of cutaneous fatty acids binding protein in head and neck squamous cell carcinoma : a molecular pathology study." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430887.
Kha, Stephanie Tieu. "An Investigation of Cellular Proliferation and Nuclear Morphology in the Multi-Step Progression of Cutaneous Squamous Cell Carcinoma." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/579258.
Bertheim, Ulf. "Impaired reparative processes in particular related to hyaluronan in various cutaneous disorders : a structural analysis." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-276.
Iannacone, Michelle R. "Case-Control Study of Sunlight Exposure and Cutaneous Human Papillomavirus Seroreactivity in Basal Cell and Squamous Cell Carcinomas of the Skin." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3164.
Gudenschwager, Basso Erwin Kristobal Felipe. "Characterization of the expression of angiogenic factors in the feline placenta during development and in feline cutaneous squamous cell carcinoma." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/97990.
PHD
Hernández, Ruiz Eugenia. "Mecanismos epigenéticos con valor pronóstico en el carcinoma escamoso cutáneo." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669702.
Cutaneous squamous cell carcinoma is the second most common skin cancer. Despite the majority of patients are diagnosed at an early stage and surgical excision is curative, about 5% of patients develop metastasis, usually to regional lymph nodes, and prognosis worsens with a 10- year overall survival of less than 20%. There are different classification systems that allow stratifying patients in function of the metastatic risk. The new American Joint Committee on Cancer classification, AJCC8, is superior in identifying high risk patients but there is much more to investigate in this field. Recently, the expression of the family of transcriptional repressors Polycomb, that silence and inactivate the genes that they regulate, have been detected in different solid tumors and it is increased in metastatic tumors. Two complexes have been identified in mammals, PCR2 or initiation complex, being EZH2 its main catalytic subunit and PRC1 or maintenance complex formed by different proteins such as RING1B and BMI1. We performed a multicentric descriptive study and 107 cutaneous squamous cell carcinomas were included; 56 metastatic carcinomas and 51 non-metastatic carcinomas that hadn´t developed metastases in a 5-year period time. In our first study we have demonstrated, using immunohistochemical stains, that EZH2 and RING1B expression is increased in metastatic cutaneous squamous cell carcinomas. In vitro functional studies using cell lines revealed that EZH2 and RING1B regulate NF-kb, since NF-kb, pathway is upregulated in Polycomb deplected cells. NF-kb, pathway is associated with inflammation. We could observe that chemotaxis of neutrophils is higher towards supernatants from cell cultures in which Polycomb proteins have been deplected. In our group of non-metastatic cutaneous squamous cell carcinomas we detected lower levels of Polycomb proteins expression using immunohistochemical stains, lower percentage of cells expressing Polycomb and lower intensity of Polycomb expression. When evaluating the inflammatory infiltrate, and despite using tissue microarrays we could also observe that non metastatic carcinomas showed higher amount of neutrophils and eosinophils in their stroma. Polycomb proteins may act silencing genes implicated in the immune response of keratinocytes and may favour the escape of tumoral cells from the immune system and the development of distant metastasis. Tumor microenvironment is not just an observer and plays an important role interacting with tumoral cells. Besides inflammatory cells, stromal fibroblasts can facilitate or inhibit tumoral cell dissemination, since they can produce different types of fibrosis with a prognostic value. Desmoplasia has always been linked to worse prognosis and some solid tumors such as pancreatic adenocarcinoma are characterized by a desmoplastic stroma which is a barrier to immune cell infiltratrion and also to chemotherapy. Ueno et al described three different types of fibrotic reaction in colorrectal carcinoma with prognostic value. In our second study we investigated the different fibrotic reaction patterns in whole hematoxilin-eosin stained sections in our series. The immature pattern characterized by myxoid changes with no inflammation was associated with tumoral budding, desmoplasia, perineural invasion, tumoral depth and metastatic risk.
Brown, Victoria Lissa. "The role of p16'I'N'K'4'a and p14'A'R'F tumour suppressor genes in the pathogenesis of cutaneous squamous cell carcinoma." Thesis, Queen Mary, University of London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423542.
Schwab, Melanie [Verfasser], and Peter [Akademischer Betreuer] Angel. "The Role of the Mucin-Like Glycoprotein Podoplanin in the Progression of Cutaneous Squamous Cell Carcinoma / Melanie Schwab ; Betreuer: Peter Angel." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/1201346436/34.
García, Díez Irene. "Estudio del perfil genómico y de expresión en carcinomas escamosos cutáneos intraepiteliales e invasivos." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/671613.
El carcinoma escamoso cutáneo (CEC) es el segundo tumor maligno cutáneo más frecuente. La mayoría de los CECs se desarrollan a partir de lesiones precursoras (queratosis actínicas ([QA]). Sin embargo, sólo una minoría de QAs evolucionan a CECs, sin que se conozcan de forma precisa los mecanismos que participan en dicha transformación. A pesar de que en la mayoría de los casos el pronóstico del CEC es excelente, existe un pequeño grupo de tumores considerados de alto riesgo (metastásicos o localmente avanzados) que presentan una evolución agresiva y mal pronóstico. En la actualidad no existen biomarcadores fiables en la práctica clínica que permitan detectar los CECs con mayor riesgo metastásico. Se ha propuesto que la expresión de PD-L1 por las células tumorales podría ser un marcador pronóstico en distintos tumores, si bien su utilidad en el CEC no ha sido previamente estudiada, distintos ensayos clínicos con nuevos fármacos dirigidos frente al eje PD1/PD-L1 en CECs han mostrado resultados esperanzadores. El objetivo de esta tesis es valorar los mecanismos moleculares implicados en las distintas etapas de la carcinogénesis del CEC (desde la piel sana fotoexpuesta [PF] hasta el CEC metastásico) con la finalidad de identificar los genes y las vías moleculares implicadas en su progresión y determinar posibles factores pronósticos. En la primera parte de este trabajo estudiamos las diferencias transcripcionales y genómicas en PFs, QAs y CECs a partir de 30 muestras apareadas por paciente, analizadas utilizando plataformas de arrays. Los resultados obtenidos se confirmaron por técnicas de RT-qPCR, inmunohistoquímica y Western blot. Identificamos dos factores de transcripción, BNC1 y FOSL1, cuya expresión se hallaba aumentada en el CEC y que podrían actuar como genes esenciales en la transformación tumoral. La integración de los datos obtenidos en los estudios de transcriptómica y de genómica reveló que las alteraciones en el número de copias del gen NEK10 se correlacionaban con los niveles de expresión de NEK10. Este gen codifica una quinasa relacionada con el gen NIMA (“Never in Mitosis gene A”), localizada dentro una región de pequeño tamaño en la banda 3p24.1, delecionada en 7 de los 10 CECs estudiados. Mediante técnicas inmunohistoquímicas y Western blot confirmamos la pérdida progresiva de la expresión de NEK10 desde la PF hasta el CEC y la práctica de estudios funcionales permitió demonstrar su participación en la regulación del ciclo celular en células epiteliales HaCaT. Todo ello apoyaría el papel de NEK10 como gen supresor tumoral en el CEC. En la segunda parte de este trabajo evaluamos el valor pronóstico de los niveles de PD-L1 en el CEC, analizando su expresión mediante inmunohistoquímica en 99 CECs primarios con metástasis linfáticas (n=48) y sin metástasis (n=51) y en 24 metástasis linfáticas. Detectamos una asociación entre la expresión de PD-L1 por ≥ 1% de las células tumorales y la presencia de metástasis linfáticas, así como con la recurrencia, una mala diferenciación histopatológica y la presencia de invasión perineural. En la mayoría de los casos (90%) existía una buena concordancia en la expresión de PD-L1 entre los CEC primarios y sus metástasis, con una tendencia hacia una mayor expresión en las últimas. No encontramos diferencias entre los tres tipos de muestras analizadas con respecto a la expresión de PD-L1 o de CD8 por las células del infiltrado peritumoral. Nuestros resultados sugieren que PD-L1 podría ser un biomarcador útil con posible valor pronóstico en el CEC.”
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Most cSCCs develop from precursor lesions (actinic keratosis [AK]). However, only a minority of AKs will eventually progress into cSCCs and the key mechanisms for this transformation remain unclear. Although in most cases the prognosis of cSCC is excellent, there is a small percentage of tumors with high metastatic risk. Metastatic or locally advanced cSCCs have high mortality, with no effective treatments available. Unfortunately, there is a lack of reliable biomarkers in clinical practice for detecting those cSCCs with the highest metastatic risk. Expression of PD-L1 by tumor cells has been proposed as a prognostic marker in different tumors. While the usefulness of PD-L1 expression in cSCC has not been addressed yet, new drugs aimed to block the PD1/PD-L1 axis are showing encouraging results in clinical trials in cSCC. The objective of this thesis is to evaluate the molecular mechanisms involved in the different stages of cSCC carcinogenesis (from healthy sun-exposed skin to metastatic cSCC) in order to identify the genes and molecular pathways involved, and their putative role as prognostic biomarkers. In the first part of this work we studied the differences in the transcriptome and the genome of sun-exposed skin, AKs and cSCCs of 30 samples matched by patient, using different array platforms. The results obtained were confirmed by quantitative RT-PCR, immunohistochemistry, and Western blot. We detected two transcription factors, BNC1 and FOSL1, whose expression was increased in cSCC and that could contribute to cSCC development. Additionally, a strong correlation between copy numbers and gene expression of NEK10 was identified by integrating the transcriptomic and genomic array data. NEK10 gene encodes a NIMA (“Never in Mitosis gene A”) related kinase, located within a small region in the 3p24.1 band, which was found to be deleted in 7 out of 10 cSCCs studied. By immunohistochemistry and Western blot, we confirmed the progressive loss of NEK10 from sun-exposed skin to cSCC and functional studies demonstrated the role of NEK10 in the regulation of the cell cycle in the epithelial HaCaT cells. These data support the role of NEK10 as a tumor suppressor gene in cSCC. In the second part of this work we evaluated the usefulness of PD-L1 expression, determined by immunohistochemistry, as a prognostic marker in cSCC. PD-L1 expression was analyzed in ninety-nine primary cSCCs with lymphatic metastases (n = 48) and without metastases (n = 51), and 24 metastases. An association between PD-L1 expression by ≥1% of tumor cells and the presence of lymphatic metastases, as well as with recurrence, poor histopathological differentiation and perineural invasion was detected. In most cases (90%), PD-L1 expression remained constant between primary cSCCs and their metastases, with a trend towards a higher expression in the latter. No differences among the three types of samples analyzed with respect to the expression of PD-L1 or CD8 by the cells of the peritumoral infiltrate were found. Our results suggest that PD-L1 could be useful as a prognostic biomarker in cSCC.
Gastaldi, Cécile. "Études des microARNs dans le développement des carcinomes spinocellulaires cutanés." Thesis, Nice, 2013. http://www.theses.fr/2013NICE4120/document.
Cutaneous squamous cell carcinomas (cSCCs) are the second most common cancer and are responsible for up to 25% of all skin cancer deaths. It is therefore essential to characterize the mechanisms responsible for epidermis carcinogenesis to develop new treatments. In this context, miRNAs appear to be prime targets for the development of future anti-tumor therapies. However, their involvement in the pathophysiology of cSCCs is still poorly documented. In this study, I identified using Small RNA sequencing, 112 miRNAs whose expression is altered during tumor development in a mouse model of cutaneous two-stage chemical carcinogenesis. Then, I focused my attention on the miR-193b/365a cluster and on miR-708, that are down-regulated during tumorigenesis, suggesting tumor suppressor functions. Consistent with this hypothesis, the ectopic expression of these miRNAs inhibit the proliferation, survival and migration of tumor cells, while blocking their action with antisense oligonucleotides stimulates these cellular functions in normal keratinocytes. Combining in silico target-prediction approaches and transcriptome analyzes of cSCC cells over-expressing these miRNAs, I identified their potential target genes. I validated KRAS and MAX as direct targets of miR-193b and miR-365a, and I showed that repression of these genes using siRNAs mimics the effects of these miRNAs. These results suggest that targeting these genes might mediate, at least in part, the tumor suppressor action of miR-193b and miR-365a in cSCCs
Tebcherani, Antonio José. "Painel imunoistoquímico para distinção entre tricoepitelioma e carcinoma basocelular desenvolvido utilizando a técnica do TMA." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5133/tde-11072012-095546/.
Trichoepithelioma is a benign neoplasm that shares both clinical and histological features with basal cell carcinoma. It is important to distinguish these neoplasms because they have different clinical behavior and require proper therapeutic planning. Many studies have addressed the use of immunohistochemistry to improve the differential diagnosis of these tumors. These studies present conflicting results when addressing the same markers, probably due to the small number of basaloid tumors that comprised their studies, which generally did not exceed 50 cases. We built a tissue microarray with 162 trichoepithelioma and 328 basal cell carcinoma biopsies and tested a panel of immune markers composed of CD34, CD10, epithelial membrane antigen, BCL-2, cytokeratins 15 and 20 and D2-40. The results were analyzed using multiple linear and logistic regression models. This analysis revealed a model that could differentiate trichoepithelioma from basal cell carcinoma in 35,9% of the cases. The panel of immunohistochemical markers required to differentiate between these tumors was composed of CD10, cytokeratin 15, cytokeratin 20 and D2-40. The results obtained in this work were generated from a large number of biopsies and resulted in the confirmation of overlapping epithelial and stromal immunohistochemical profiles from these basaloid tumors. The results also corroborate the point of view that trichoepithelioma and basal cell carcinoma tumors represent two different points in the same line of differentiation. Despite the use of panels of immune markers, histopathological criteria associated with clinical data certainly remain the best guideline for the differential diagnosis of trichoepithelioma and basal cell carcinoma
Silva, Ana Paula da. "Avaliação histopatológica do tratamento do carcinoma espinocelular cutâneo em camundongos usando terapia fotodinâmica mediada por azul de metileno." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-25112014-130952/.
Photodynamic therapy (PDT) is a clinical method for treating a variety of tumors, skin disorders and represents a promising cosmetic treatment. This study evaluated the histopathological and molecular aspects of the treatment by PDT mediated by methylene blue (PDT-MB) in vivo experimental model of cutaneous squamous cell carcinoma (SCC) and in healthy skin of swiss mice. The PDT protocol was a single session with the application of MB 1% solution followed by irradiation with diode laser at a total dose of 24 J/cm2 in tumor and healthy tissue. The animals were sacrificed at two periods, 24 hours and 15 days after PDT. Morphological changes were less marked in the tumor tissues treated, however, were more pronounced in healthy tissues treated. We can conclude that the effects of a single session of PDT mediated by MB in applied dose conferred no improvement in the treatment of SCC. These results motivate further studies with adjustments in the protocol to improve the effectiveness of this therapy.
Guim, Tainã Normanton. "Avaliação da sobrevida e de marcadores histomorfológicos como potenciais fatores prognósticos para carcinoma de células escamosas em cães e gatos." Universidade Federal de Pelotas, 2010. http://repositorio.ufpel.edu.br/handle/ri/2558.
Squamous cell carcinoma (SCC) is a cutaneous malignant neoplasm commonly observed in dog and cat. Especially in our country, the SCC represents a serious problem, since chronic exposure to ultraviolet radiation is one of the important factors for the development of the disease. In this way, the objective of this study was establish histomorphological markers as prognostic factors and determine the time and the estimated survival of dogs and cats carriers of SCCs. A survey of cases of SCCs in dog and cat diagnosed at the Regional Diagnostic Laboratory from the Federal University of Pelotas, was performed during the period of 1999 to 2009. Fifty samples were obtained from biopsies and/or necropsies. From the studied cases, 24 animals with the disease were followed for a period of one year. In this study, we used the histological grade and survival time of animals as a criterion to prognostic evaluation. The histological parameters evaluated as peritumoral lymphoplasmacytic infiltration, tissue eosinophilia associated with tumor, mitotic index, arrangement, invasion to adjacent tissues, emboli vascular blood and/or lymphatic, desmoplastic reaction and quantification of AgNORs were confronted with the histological grade and the survival time of affected animals. When the histological parameters were compared with survival, a significant relation was observed with the intensity of invasion to adjacent tissues (p <0.05). When confronted with the histological grade, the invasion show significant results only to poorly differentiated SCCs and desmoplasia were statistically significant (p <0.05). In this study, the estimate of survival was 23.4% in one year to animals with or without treatment. From the results obtained, it was concluded that the intensity of invasion is an important predictive prognostic factor for cutaneous SCCs in dogs and cats. Other parameters showed no relation with the histological grade and/or survival, thus, are not considered prognostic factors predictive. The time and the estimate of survival were low and therefore the prognosis for dogs and cats carrier of cutaneous SCCs is unfavorable.
Carcinoma de células escamosas (CCE) é um neoplasma cutâneo maligno comumente observado no cão e no gato. Especialmente em nosso país, o CCE representa um problema sério, uma vez que a exposição crônica à radiação ultravioleta é um dos fatores importantes para o desenvolvimento da doença. Neste sentido, o presente estudo teve como objetivo estabelecer marcadores histomorfológicos como fatores prognósticos e determinar o tempo e a estimativa de sobrevida de cães e gatos portadores de CCEs cutâneos. Foi realizado um levantamento dos casos de CCEs em cães e gatos diagnosticados no Laboratório Regional de Diagnóstico da Universidade Federal de Pelotas, durante o período de 1999 a 2009. Foram recuperadas 50 amostras provenientes de biópsias e/ou necropsias. Do total de casos estudados, 24 animais portadores da doença foram acompanhados durante um período de um ano. Neste estudo, utilizou-se o grau histológico e o tempo de sobrevida como critério de avaliação prognóstica. Os parâmetros histológicos avaliados como: infiltrado linfoplasmacítico peritumoral, eosinofilia tecidual associada a tumores, índice mitótico, arranjo, invasão para tecidos adjacentes, êmbolo vascular sanguíneo e/ou linfático, desmoplasia e quantificação das AgNORs, foram confrontados com o grau histológico e com a sobrevida dos animais acometidos. Quando os parâmetros histológicos foram confrontados com a sobrevida, observou-se relação estatística significativa com a intensidade de invasão para tecidos adjacentes (p<0,05) e, quando confrontados com o grau histológico, a invasão somente para CCEs pouco diferenciados e a desmoplasia foram estatisticamente significativos (p<0,05). No presente estudo, a estimativa de sobrevida para animais portadores de CCEs cutâneos foi 23,4% em um ano, independentemente de terem sido tratados ou não. A partir dos resultados obtidos, concluiu-se que a intensidade de invasão é um fator prognóstico preditivo importante para CCEs cutâneos em cães e gatos. Os demais parâmetros avaliados não mostraram relação com o grau histológico e/ou com a sobrevida, dessa forma, não são considerados fatores prognósticos preditivos. O tempo e a estimativa de sobrevida foram baixos e, portanto, o prognóstico para cães e gatos portadores de CCEs cutâneos é, de um modo geral, desfavorável.
Simonneau, Marie. "Implication de l'Oncostatine M dans la genèse et le développement des carcinomes épidermoïdes cutanés." Thesis, Poitiers, 2018. http://www.theses.fr/2018POIT1403/document.
Cutaneous squamous cell carcinoma (cSCC) is one of the most frequent keratinocyte malignancies worldwide and is chemotherapy resistant. Surgery is the curative treatment but there isn’t any alternative in advanced cSCC. Reprogramming tumor microenvironment and tumor immunosuppressive mechanisms is a new therapeutic approach. Indeed, depending on cytokine expressed in tumor microenvironment, immune cells can inhibit (Th1/M1 cells) or enhance (Th2/M2 cells) tumor development. It was previously showed that Onconstatin M (OSM) had pleiotropic effects on cancer cells. OSM can promote cancer by inducing tumor cells motility, invasiveness or by reprogramming immune cells toward a more permissive phenotype (M2 polarization). Our previous data showed that OSM has proinflammatory effects on skin and modulate normal keratinocyte phenotype both in vitro and in vivo. In this study, we hypothesized that OSM could be involved in cSCC development. We showed that OSM was overexpressed in human cSCC as well as other cytokines such as IL-6, IL-1β, IFNγ whereas IL-4 was decreased, suggesting a Th1/M1 polarization of cSCC microenvironment. In vitro, OSM induced STAT-3 and ERK signalization, modified gene expression, promoted proliferation and migration of malignant keratinocyte PDVC57 cells. PDVC57 cells grafted in skin mice led to cSCC development associated to OSM overexpression by immune infiltrated cells. Finally, we showed that the absence of OSM led to a 30% reduction of tumor size and reduced M2 polarization in tumor microenvironment. Collectively, these results support a pro-tumoral role of OSM in cSCC development and suggest a new therapeutic approach targeting this cytokine
Strioga, Marius. "Expression of biomarkers, representing immunosuppressive, cytotoxic or immunomodulating properties of CD8h T lymphocytes in the peripheral blood of patients with immunogenic cancer forms." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2010~D_20100702_105111-42651.
Darbo tikslas buvo įvertinti imunosupresines (FOXP3, NKG2A), citotoksines (perforin) bei citotoksines / imunomoduliuojančias (IFNγ) savybes atspindinčių žymenų raiškos skirtumus išplitusiu inkstų vėžiu ar didelės rizikos odos melanoma sergančių pacientų periferinio kraujo CD8h T limfocitų populiacijoje, lyginant su kontroline grupe. Skirtingas T limfocitų savybes atspindinčių žymenų raiška buvo tiriama tėkmės citometrijos būdu. Nustatyta, kad inkstų vėžiu ar odos melanoma sergančių pacientų periferiniame kraujyje Įvairių subpopuliacijų (ypač imunosupresinės) nuošimčio nustatymas CD8hCD57+ T limfocitų populiacijoje ateityje gali būti naudingas klinikinėje praktikoje, individualizuojant priešnavikinę imunoterapiją ir selektyviai parenkant tik tuos pacientus, kuriems imuninės sistemos aktyvinimas sukeltų navikinių ląstelių naikinimą, o ne dar labiau gilintų imunosupresiją.
Strioga, Marius. "Imunosupresines, citotoksines bei imunomoduliuojančias savybes atspindinčių žymenų raiška imunogeniškomis vėžio formomis sergančių pacientų periferinio kraujo CD8h T limfocitų populiacijoje." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2010~D_20100702_105125-92547.
The aim of the study was to evaluate the expression of immunosuppressive (FOXP3, NKG2A), and cytotoxic (perforin) or cytotoxic / immunomodulating (IFNγ) T-cell properties representing biomarkers in the peripheral blood CD8h T-cell population of patients with advanced renal cell carcinoma (RCC) or high risk cutaneous melanoma and healthy controls by multicolour flow cytometry. Determination of the percentage of functionally competing T-cell subsets (especially immunosuppressive) in the CD8hCD57+ T-cell subpopulation in future may serve as one of parameters enabling to assess the overall status of antitumor immune response and select cancer patients most suitable for antitumor immunotherapy while dismissing those to whom it would be ineffective or even harmful.
Maubec, Eve. "Prédisposition génétique au mélanome : de la génétique à la recherche clinique." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T034.
This thesis had two main objectives: 1) To define groups of patients which may benefit from genetic counseling by identifying predictors of mutations of the CDKN2A gene, a major gene predisposing to cutaneous melanoma (CM) in families with only two cases. 2) Epidemiological and clinical characterization of specific entities of melanoma with the secondary objective of contributing to the identification of susceptibility genes for these entities. Coexistence of CM with renal cell carcinoma and mucosal anogenital melanomas were studied.The study populations are a collection of 293 melanoma patients that were ascertained systematically and the French collection MELARISK which is a collection including over 3000 subjects drawn from families with multiple cases of melanoma or melanoma occurring in a particular context (association with another cancer, rare locations, occurrence before the age of 20, multiple sporadic melanomas).We investigated association of three clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 versus ≥3 CM patients among first-degree relatives in a family).The study was conducted in 483 French families including 387 families with two melanoma patients, and 96 families with three or more patients with melanoma. The factors examined individually and in a joint analysis in a family were: median age at diagnosis <50 years, ≥1 patient in a family with multiple primary melanomas (MPM) or with pancreatic cancer. The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). While early age at melanoma diagnosis and occurrence of MPM in ≥1 patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families. Thus this study showed that clinical features associated with CDKN2A mutations vary, in France, a country of low incidence of melanoma, according to the degree of familial clustering. Identifying predictors of CDKN2A mutations in families with two melanoma cases has helped to define subgroups of families (early age at CM diagnosis, and/or ≥1 MPM patient) in which the frequency of CDKN2A mutations is above 20% such that these subgroups of F2 families should be offered genetic testing.The analysis of two series of patients, either patients with melanoma coexisting with renal cell carcinoma or patients with anogenital mucosal melanoma identified their clinical and histological features by comparing them to a series of melanomas that were ascertained systematically. In both series, our results suggested a genetic predisposition at least partly independent of CDKN2A. The study of the c renal cell carcinoma; coexistence of CM and renal cancer in the same patient had two practical consequences for clinicians: it suggests the interest of a dermatologic screening visit in patients with renal cell carcinoma and that abdominal ultrasonography or computed tomography scanning performed at the initial workup and during the follow-up of patients with CM may be of value for the early detection of renal cancer. Regarding genetic research, this series has contributed to the identification of a germline mutation in the MITF gene that increases the risk of developing melanoma, renal cancer or both cancers and has interesting biological properties. The study of anogenital melanoma has shown that these melanomas could be associated with cutaneous melanoma in the same patient and it has also shown a high frequency of family history of melanoma associating mucosal and CM suggesting a shared genetic predisposition. Consequently dermatological screening or monitoring must include examination of both skin and mucosa in families with multiple cases of CM; and in case of a mucosal melanoma, a dermatological examination should be offered to relatives. The genetic mechanism has to be identified
Colas, Victor. "Modeling and estimation of human skin optical properties using spatially resolved autofluorescence and diffuse reflectance spectroscopy." Electronic Thesis or Diss., Université de Lorraine, 2022. http://www.theses.fr/2022LORR0129.
In the context of cutaneous carcinoma, optical biopsy offers a in-vivo non-destructive alternative to conventional biopsy to inform the dermatologist of the state of health of the deep tissue during cancer resection. The latter is indeed at the origin of morphological and physiological modifications of the skin, which explains why the optical measurements resulting from the light/tissue interactions are sensitive to it. The work presented in this manuscript exploits the data obtained with the optical biopsy device extit{SpectroLive} on about a hundred patients just before cancer resection by the clinician. In contact with the skin, this spectroscopic device acquires diffuse reflectance (white broadband excitation) and autofluorescence (monochromatic emission to excite endogenous fluorophores in the skin) spatially resolved signals, extit{i.e.}, for several separation distances between the light emitting fiber and the collecting fibers at the periphery. This spatial resolution is of particular interest for the skin, since the different distances introduced allow the collection of photons traveling through the different layers in depth (epidermis, dermis and hypodermis) of the organ. The main part of the work presented here concerns the estimation of the optical properties of the skin by solving the inverse problem from these clinical acquisitions. This consists first in establishing a photon transport simulation faithful to the characteristics (geometrical and spectral) of the real device before building a multilayer model of the skin in which the optical parameters (e.g. absorption and scattering coefficients, the anisotropy factor) and geometrical parameters e.g. layer thickness) can be estimated by an optimization process aiming at minimizing the differences between the spectra generated by the simulation and the ``target'' spectra obtained in clinic. The main contributions developed in this manuscript are first the development and the full exploitation of the simulation, with in particular a study whose purpose is to characterize the penetration of the photons detected at the various source/detector separations, and this for various skin models in order to represent the inter- and intra-individual differences. The knowledge acquired with this study of probed depths is then used in the second major contribution, aiming at adapting the process of estimating optical properties from clinical spectra (inverse problem) to the skin. Finally, the last contribution, more metrological, is the development of an optical bench with double integrating spheres allowing to obtain these same optical properties for a sample ex-vivo, and thus to allow the comparison of the estimates resulting from the two modalities
Akinduro, Olufolake A. E. "Autophagy in epidermis." Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8703.
Khou, Sokchea. "Contribution des neutrophiles infiltrant les tumeurs dans la progression des carcinomes épidermoïdes cutanés : neutrophiles et cancer." Thesis, Université Côte d'Azur (ComUE), 2019. http://theses.univ-cotedazur.fr/2019AZUR4014.
Non-melanoma skin carcinomas are the most frequent cancers in Human and their incidence is constantly increasing. Two main types exist: the cutaneous basal cell carcinoma (cBCC) and the cutaneous squamous cell carcinomas (cSCC). Risk factors include sun radiation and immunosuppression. These cancers are mainly treated with surgery and radiotherapy but they can reach an incurable stage. For this reason, novel therapeutic alternatives are needed. At present, immunotherapies constitute a revolution in the treatment of cancers. Its mechanism of action relies on the stimulation of the immune system of cancer patients, so that they develop efficient anti-tumoral immune responses. cSCC may benefit from this type of treatment as they generally develop in the context of an immunosuppression. Immune surveillance involves both immune cells and the tumor microenvironment, in particular the stroma. During the elimination phase, the anti-tumoral responses, mediated mainly by CD8+ T lymphocytes, are efficient. Then, there is an equilibrium phase in which the tumor is stable before the escape phase, when the tumor can evade immune surveillance and grow. Our research interest focused on neutrophils, a subset of myeloid cells that are very rapidly recruited to the sites of inflammation and inside tumors. A recent meta-analysis of 39 human malignancies showed that neutrophils are associated with the worst clinical outcome. Neutrophils harbor both anti- and pro-tumoral functions. This polarization seems to be dependent on type I interferon and TGF-β, respectively. It remains to establish the exact role played by neutrophils in cancer and specifically in skin carcinomas. The aim of our research was to further characterize the functions and the contribution of neutrophils to the development of cutaneous squamous cell carcinomas. We first used a chemically-induced skin carcinoma mouse model that recapitulates the different stages of skin carcinoma development in Human. In this model, we saw a massive infiltration of neutrophils at the precancerous and cancerous stages. We performed transcriptomic analysis of highly purified neutrophil populations from precancerous, cancerous lesions and from the surrounding skin controls. These data revealed a specific gene signature in neutrophils from lesions compared to surrounding skins. Differential gene expression analysis identified a pro-tumoral phenotype for neutrophils infiltrating lesions compared to skins. In a second approach, we studied the growth of a cSCC cell line grafted in the dermis of mice. Specific depletion of neutrophils significantly delayed tumor growth, thus indicating that neutrophils were pro-tumoral. Mechanisms of action included the production of ROS and NO that favor tumor growth and the immune suppression of anti-tumoral responses mediated by tumor-associated CD8+ T cells. In the tumor, neutrophils produced arginase 1 which catalyzes the degradation of arginine, thus inhibiting the proliferation of CD8+ T cells. In addition, we found that the tumor microenvironment induced PD-L1 expression at the cell surface of neutrophils and concomitantly, PD1 on CD8+ and CD4+ T cells. These results suggested that PD-L1/PD1 interaction triggers immune suppression and contributes to SCC progression. Indeed, a positive and significant correlation was observed between tumor size and frequencies of PD-L1-expressing neutrophils inside tumors. Collectively, these results suggest that it is relevant to assess immunotherapies that block PD-L1/PD1 interaction for the treatment for cSCC. These approaches could be combined with treatments that aim to block the recruitment or inhibit neutrophils. Moreover, it remains to evaluate whether the frequency of PD-L1-expressing neutrophils could constitute a good predictive marker of the response to anti-PD-L1 and anti-PD1 immunotherapies
ARFI, CATHERINE. "Exerese en deux temps des carcinomes cutanes etendus de la face : etude retrospective de 87 patients." Nantes, 1994. http://www.theses.fr/1994NANT247M.
PIREDDU, ROSA. "Nanosized systems for efficient delivery of antitumoral and anti-inflammatory drugs." Doctoral thesis, Università degli Studi di Cagliari, 2015. http://hdl.handle.net/11584/266618.
ROCA, ROUSSEAUX FREDERIQUE. "Actualites en cryochirurgie : que penser d'un nouveau cryogene, le protoxyde d'azote, dans le traitement des carcinomes cutanes ? apport de l'echographie cutanee, mode b, comme nouvelle methode de controle." Reims, 1992. http://www.theses.fr/1992REIMM033.
Pyczek, Joanna. "Hedgehog signaling in cutaneous squamous cell carcinoma." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-002E-E330-0.
Laert, José Artur Veiga. "Revisão sistemática: tratamento do carcinoma espinocelular cutâneo avançado." Master's thesis, 2019. http://hdl.handle.net/10316/89850.
INTRODUÇÃO: O carcinoma espinocelular cutâneo (CECc) é o segundo tipo mais comum de neoplasia da pele e a sua incidência tem vindo a aumentar ao longo das últimas décadas. A maioria dos CECc pode ser tratada com procedimentos simples, no entanto o tratamento da doença avançada está mal definido e, pela sua raridade, existem poucos ensaios clínicos disponíveis. Esta revisão sistemática tem como objetivo sumarizar as opções de tratamento disponíveis, focando nos avanços mais recentes. MÉTODOS: Foram realizadas pesquisas nas bases de dados PubMed e Embase utilizando palavras-chave relacionados com o CECc avançado. Aplicando critérios específicos de inclusão e exclusão, a seleção dos artigos foi efetuada com base na leitura do título e/ou resumo. Também se consideraram elegíveis as recomendações internacionais sobre o tema.RESULTADOS: Obtiveram-se 80 artigos publicados entre 2010 e 2018. Cirurgia, radioterapia e quimioterapia, isoladas ou em associação, têm sido considerados o tratamento padrão do CECc avançado. A deteção de mutações das vias de proliferação celular abriu as portas ao uso das terapêuticas dirigidas a alvos moleculares, nomeadamente os inibidores do EGFR. A elevada carga mutacional torna estes tumores suscetíveis de responder à imunoterapia.DISCUSSÃO: Os resultados obtidos com cirurgia, radioterapia e quimioterapia são condicionados pelo grau de evolução da doença, sendo a sua aplicação limitada pelas comorbilidades dos doentes. Os inibidores do EGFR estão associados a respostas objetivas relevantes, embora de curta duração. Em relação à imunoterapia, os estudos iniciais sobre os inibidores do PD-1 mostram uma taxa de resposta significativa. CONCLUSÃO: A escassez de estudos controlados para confirmar a eficácia e segurança das terapêuticas disponíveis dificulta uma estandardização do tratamento baseada em evidência robusta. Apesar das novas opções terapêuticas, o CECc avançado permanece uma doença de mau prognóstico.
INTRODUCTION: Cutaneous squamous cell carcinoma is the second most common type of skin neoplasm and its incidence has been increasing over the last decades. Most cases can be treated with simple procedures, but the treatment of advanced disease is poorly defined and, due to its rarity, there are few clinical trials available. This systematic review aims to summarize the available treatment options, focusing on the most recent advances in this field.METHODS: A search was performed on PubMed and Embase databases using keywords related to advanced cutaneous squamous cell carcinoma. Applying specific inclusion and exclusion criteria, the selection of the articles was done based on the reading of the title and/or summary. International recommendations on the subject were also considered eligible.RESULTS: A total of 80 articles published between 2010 and 2018 have been found. Surgery, radiation therapy and chemotherapy, alone or in association, have been considered the standard treatment for advanced cutaneous squamous cell carcinoma. Detection of mutations in cell proliferation pathways has opened the doors to the use of targeted therapies, namely EGFR inhibitors. The high mutational burden serves as a rational basis for the use of immune checkpoint inhibitors.DISCUSSION: The results obtained with surgery, radiotherapy and chemotherapy are conditioned by the degree of the disease, and its application is limited by the patients comorbidities. EGFR inhibitors are associated with a significant rate of disease control, but the response is generally short-lived. Regarding immunotherapy, initial studies on PD-1 inhibitors show a significant response rate.CONCLUSION: Considering the few controlled studies to confirm the efficacy and safety of different treatments, it is still not possible to design an evidence-based standard management of this disease. Advanced cutaneous squamous cell carcinoma is a disease with poor prognosis despite the new therapies.
Hsiang-YunWang and 王湘韻. "PEI-mediated Anti-cancer Gene Delivery to Cutaneous Squamous Carcinoma Cell." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/54803070449885568583.
國立成功大學
臨床藥學與藥物科技研究所
100
Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer. The incidence of this type of skin cancer has increased greatly for the past decade. The treatment for treatment of squamous cell carcinoma include surgery, radiotherapy, chemotherapy, immunotherapy and gene therapy. Human WWOX gene, encoding the WWOX/FOR/WOX1 family proteins, is mapped to a fragile site on chromosome 16q23.2. WOX1 protein is considered as a candidate tumor suppressor protein. TP53 gene is located on the short arm of chromosome 17p13.1. It is well-known that p53 protein is important for cellular response to a wide variety of stressful stimulation. During the development of skin cancer, loon-term ultraviolet radiation (UVR) exposure can alter gene activity in keratinocytes, resulting notably p53 mutantion. The technology of gene delivery plays an important role in the evelopment of gene therapy. Several methods have been developed to transfer DNA into cells for gene therapy. One of the non-invasive gene delivery methods is the use of gene vectors or carriers. Polyethylenimine (PEI) is a cationic polymer-based gene carrier,. Many researches demonstrated that PEI can transfer genes into different kind of cells under different transfection conditions. The aim of this study was to examine the feasibility of using PEI as gene carrier to deliver WWOX gene TP53 gene to squamous cell carcinoma. The PEI/DNA complexes of different N/P ratios were characterized by gel retardation assay. Transfection efficiency, degree of cell apoptosis and protein expression were analyzed in SCC cells and HaCaT cells, in order to determine optimal transfection conditions for PEI/DNA complexes to be used in in vivo experiments. Results of gel retardation assay showed that WWOX gene formed complexes with PEI when N/P ratios were greater than 4:1. It was demonstrated that transfection efficiency were related to the amount of DNA, but not to DNA types in both cell lines, and transfecton efficiency of PEI was lower than that of Lipofectamine. In SCC-15 cells, degree of apoptosis induced by WWOX gene were not related with DNA types. However, degree of apoptosis induced by p53 gene were dose-dependent. On the other hand, degree of apoptosis induced by both WWOX gene and p53 gene in HaCaT cell was associated with DNA content but not with DNA types. Degree of apoptosis induced by PEI/DNA complex was more prominent than lipo/DNA complex in HaCaT cells, while they were comparable in SCC-15 cells. Based on the above data, vector/DNA 2μg/mL (N/P ratio 8:1) was selected for the following evaluation. The results displayed that WWOX protein expression was significantly increased in comparison with control groups in both cell lines. For HaCaT cell, protein expression level was comparable between PEI and Lipo as vectors, while in SCC-15 Cell, protein expression level by PEI-mediated gene delivery was greater than Lipo. Direct injection of vector/DNA complexes into tumor-bearing mice demonstrated that PEI/WWOX pEGFPC1, PEI/WWOX-pEGFPC1+ PEI/p53-pDsRedN1, Lipo/WWOX-pEGFPC1 and PEI/p53-pDsRedN1 complexes significantly inhibited tumor growth in comparison to the control. Among these groups, the effect from PEI/WWOX-pEGFPC1 complex was the most prominent. In summary, the current study demonstrated that both WWOX gene and p53 gene can be effectively delivered to squamous cell carcinoma by PEI and Lipofectamine and effectively reduced tumor size in vivo. The effect of PEI was comparable to Lipofectamine in terms of transfection efficiency, apoptotic effect and protein expression, with the advantages of easy accessibility and cost-effectiveness. It is concluded PEI with WWOX gene and p53 gene complexes is a potential therapeutics for squamous cell carcinoma. Keywords:Squamous cell carcinoma (SCC), WWOX gene, p53 gene, gene delivery, polyethylenimine(PEI)
Frydenlund, Noah. "Neurotrophin receptors in select cutaneous malignancies with a propensity for perineural invasion." Thesis, 2015. https://hdl.handle.net/2144/16317.
Pinho, António Álvaro Pereira de. "Association of Human Papillomavirus with Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: a systematic review and meta-analysis." Master's thesis, 2018. https://hdl.handle.net/10216/111949.
Pinho, António Álvaro Pereira de. "Association of Human Papillomavirus with Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: a systematic review and meta-analysis." Dissertação, 2018. https://repositorio-aberto.up.pt/handle/10216/111949.
Khizanishvili, Natalia. "The role of Hedgehog signaling and its interaction with EGFR-pathway in cutaneous squamous cell carcinoma." Doctoral thesis, 2020. http://hdl.handle.net/21.11130/00-1735-0000-0005-1427-9.
Batista, Cheila Daniela Andrade. "Imunoterapia no Tratamento do Carcinoma Espinhocelular Avançado." Master's thesis, 2021. http://hdl.handle.net/10316/98402.
O carcinoma espinhocelular apresenta uma incidência crescente e mortalidade significativa quando em estado avançado, razão pela qual o seu tratamento tem especial relevância. O CEC avançado representa os tumores localmente avançados (irressecáveis) ou metastáticos, em que a excisão cirúrgica não permite a cura, determinando outras abordagens terapêuticas. Até recentemente, a quimioterapia tinha o papel preponderante, ainda que limitado, devido aos efeitos adversos graves. Entretanto surgiram os inibidores EGFR, anticorpos dirigidos ao recetor do fator de crescimento epidérmico, que têm uma atividade limitada comparativamente à quimioterapia, apesar de um perfil de toxicidade mais benéfico. A radioterapia e a eletroquimioterapia são também opções consideráveis mas nem sempre aplicáveis. Assim, foi necessário desenvolver alternativas mais seguras e eficazes no tratamento de doentes em estado avançado.Nas últimas décadas, surgiu um novo paradigma terapêutico, com base em anticorpos monoclonais e pequenos inibidores moleculares que bloqueiam vias de sinalização envolvidas na patogénese tumoral e no checkpoint imunitário. A supressão da imunomodulação negativa é, assim, um dos grandes pilares atuais da imunoterapia. De facto, o CEC é dos cancros que possui um maior número cumulativo de mutações, carga mutacional esta que se reflete na boa resposta à imunoterapia.Entre os diferentes imunoterápicos, destacam-se os inibidores PD-1. Estes fármacos têm afinidade para o recetor-1 de morte celular programada (PD-1), impedindo a sua ligação aos ligandos PD-L1 e PD-L2 expressos pelas células tumorais, o que causaria a inibição funcional das células T. Deste modo, a resposta citotóxica antitumoral é potenciada, controlando a proliferação tumoral. Estes fármacos apresentam um perfil de toxicidade bastante favorável.Em 2018, assiste-se à aprovação, pelas FDA e EMA, do primeiro inibidor PD-1 destinado ao tratamento de CEC avançado, o cemiplimab. Recentemente, em 2020, foi também aprovado pela FDA o pembrolizumab. Outros fármacos desta categoria estão atualmente a ser testados.No futuro, será importante o estudo dos indicadores preditores de resistência ou de boa resposta a estes agentes, tal como a carga mutacional. Também a utilidade da imunoterapia nos indivíduos transplantados deve ser um importante objeto de investigação, assim como a combinação da imunoterapia com outras abordagens, inclusive a nível neoadjuvante / adjuvante.A imunoterapia veio abrir novas portas no tratamento do CEC avançado, apresentando um boa relação benefício-risco, sendo da maior importância a análise de todo o seu potencial.
Cutaneous squamous cell carcinoma (cSCC) has an increasing incidence and significant mortality when at advanced stage, which is why its treatment is particularly relevant. Advanced cSCC represents locally advanced (unresectable) or metastatic tumors, in which surgical excision does not allow a cure, determining other therapeutic approaches.Until recently, chemotherapy had a predominant role, albeit limited, due to serious side effects. Meanwhile, EGFR inhibitors, antibodies directed to the epidermal growth factor receptor, have a limited activity compared to chemotherapy, despite a more beneficial toxicity profile. Radiotherapy and electrochemotherapy are also considerable options, but not always applicable. Thus, it was necessary to develop safer and more effective alternatives in the treatment of advanced patients.In the last few decades, a new therapeutic paradigm has emerged, based on monoclonal antibodies and small molecular inhibitors that block signaling pathways involved in tumor pathogenesis and the immune checkpoint. The suppression of negative immunomodulation is thus one of the great pillars of immunotherapy today. In fact, CEC is one of the cancers that has a greater cumulative number of mutations, which is reflected in the good response to immunotherapy.Among the different immunotherapeutic agents, PD-1 inhibitors stand out. These drugs have an affinity for the programmed cell death receptor-1 (PD-1), preventing their binding to the PD-L1 and PD-L2 ligands expressed by tumor cells, which would cause functional inhibition of T cells. Thus, antitumor cytotoxic response is enhanced, controlling tumor proliferation. These drugs have a very favorable toxicity profile.In 2018, FDA and EMA approved the first PD-1 inhibitor for the treatment of advanced cSCC, cemiplimab. Recently, in 2020, pembrolizumab was also approved by FDA. Other drugs in this category are currently being tested.In the future, it will be important to study the predictive indicators of resistance or good response to these agents, such as the mutational burden. Also, the usefulness of immunotherapy in transplanted individuals should be an important research goal, as well as the combination of immunotherapy with other approaches, including at the neoadjuvant / adjuvant level.Immunotherapy has opened new doors in the treatment of advanced CPB, presenting a good risk-benefit ratio, and the analysis of its full potential is of utmost importance.