Дисертації з теми "Programmed cell death ligand 1"
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Murata, Daiki. "High programmed cell death 1 ligand-1 expression: association with CD8+ T-cell infiltration and poor prognosis in human medulloblastoma." Kyoto University, 2018. http://hdl.handle.net/2433/233841.
Повний текст джерелаLiu, Bin. "PD-1/PD-L1 expression in a series of intracranial germinoma and its association with Foxp3+ and CD8+ infiltrating lymphocytes." Kyoto University, 2018. http://hdl.handle.net/2433/233842.
Повний текст джерелаHamanishi, Junzo. "Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer." Kyoto University, 2009. http://hdl.handle.net/2433/124273.
Повний текст джерелаMcKendry, Richard. "Expression and function of programmed cell death Protein-1 (PD-1) and ligand PD-L1 in Chronic Obstructive Pulmonary Disease." Thesis, University of Southampton, 2014. https://eprints.soton.ac.uk/385139/.
Повний текст джерелаSampangi, Sandeep. "Autologous human kidney proximal tubule epithelial cells (PTEC) modulate dendritic cell (DC), T cell and B cell responses." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/82033/1/Sandeep_Sampangi_Thesis.pdf.
Повний текст джерелаvan, der Linde Lea Isabell Shari [Verfasser], Lutz [Akademischer Betreuer] Welker, and Bernhard [Akademischer Betreuer] Schaaf. "Programmed Cell Death-Ligand 1 : Beitrag der Zytologie zur zielgerichteten Therapie von Lungenkarzinomen / Lea Isabell Shari van der Linde ; Akademische Betreuer: Lutz Welker, Bernhard Schaaf." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1228131252/34.
Повний текст джерелаWise, Randi. "The role of the secretory pathway and cell surface proteolysis in the regulation of the aggressiveness of breast cancer cells." Diss., Kansas State University, 2017. http://hdl.handle.net/2097/38199.
Повний текст джерелаBiochemistry and Molecular Biophysics Interdepartmental Program
Anna Zolkiewska
Cancer cells exploit key signaling pathways in order to survive, proliferate, and metastasize. Understanding the intricacies of the aberrant signaling in cancer may provide new insight into how to therapeutically target tumor cells. The goal of my research was to explore the role of two modulators of transmembrane signaling, the secretory pathway and cell surface proteolysis, in the aggressiveness of breast cancer cells. To study the role of the secretory pathway, I focused on the family of endoplasmic reticulum (ER) chaperones. I found that several ER chaperones were upregulated in breast cancer cells grown under anchorage-independent conditions as mammospheres versus those grown under adherent conditions. Furthermore, certain members of the protein disulfide isomerase (PDI) family were consistently upregulated in two different cell lines at both the mRNA and protein levels. Knocking down these PDIs decreased the ability of the cells to form mammospheres. I demonstrated that the requirement for PDI chaperones in mammosphere growth is likely due to an increased flux of extracellular matrix (ECM) components through the ER. Next, I examined the role of cell surface proteolysis in modulating the aggressiveness of breast cancer cells. Cell-surface metalloproteases release soluble growth factors from cells and activate the corresponding growth factor receptors. I determined that specific metalloproteases (ADAM9 or ADAM12), modulate the activation of Epidermal Growth Factor Receptor (EGFR). I demonstrated that EGFR activation enhances the CD44⁺/CD24⁻ cell surface marker profile, which is a measure of cancer cell aggressiveness. I found that the MEK/ERK pathway, which is a downstream effector of EGFR activation, modulates the CD44⁺/CD24⁻ phenotype. When DUSP4, a negative regulator of the MEK/ERK pathway, is lost, activation of EGFR by metalloproteases no longer plays a significant role in cancer cell aggressiveness. This indicates that the ligand dependent activation of the EGFR/MEK/ERK pathway is a critical step in DUSP4-positive aggressive breast cancer. Finally, I examined the importance of metalloproteases in the regulation of Programmed-death ligand 1 (PD-L1), a transmembrane protein expressed by some cancer cells that plays a major role in suppressing the immune system. I demonstrated that cell-surface metalloproteases have the ability to cleave PD-L1 and release its receptor-binding domain to the extracellular environment. Collectively, these data indicate that (a) ER chaperones support anchorage-independent cell growth, (b) metalloproteases are important in regulation of an aggressive phenotype through the EGFR/MEK/ERK pathway, and (c) metalloproteases cleave PD-L1, a key component of immunosuppression in cancer.
Richmond, Owen Benjamin. "Immune modulation mechanisms of porcine circovirus type 2." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/73766.
Повний текст джерелаPh. D.
Sonnenburg, Anna [Verfasser]. "Optimierte In-vitro-Testung von Fremdstoffen auf hautsensibilisierendes Potenzial durch CRISPR/Cas9-vermittelten Knockout des Arylhydrocarbon-Rezeptors und Antikörperblockade des inhibitorischen Moleküls programmed cell death-ligand 1 / Anna Sonnenburg." Berlin : Freie Universität Berlin, 2021. http://d-nb.info/1238595820/34.
Повний текст джерелаAcheampong, Emmanuel. "Assessment of circulating tumour cells in lung cancer patients." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2022. https://ro.ecu.edu.au/theses/2554.
Повний текст джерелаStephen, Victor Emmanuel. "Deciphering the immune response to respiratory pathogens - Role of programmed death-ligand 1." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066249/document.
Повний текст джерелаSummaryPulmonary infections caused by respiratory pathogens are among the major causes of death worldwide. The outcome of infection depends on the ability of the host to respond to the challenge posed by the pathogens. Of note, the host needs to sense the pathogen, mount an efficient immune response and finally clear the ensuing inflammatory response to avoid tissue damage. In this context pathogens have adapted numerous strategies that hijack the host mechanisms to dampen the immune response and as a consequence causing infection. The programmed death-ligand 1 (PD-L1) – programmed death 1 (PD-1) pathway is a key pathway involved in mediating self-tolerance thereby maintaining homeostasis. Elegant reports have demonstrated that the PD-L1 – PD-1 pathway is exploited by cancer cells and viruses as an immune evasion mechanism to suppress effector T cell responses. Thus, I aimed at investigating the role of PD-L1 pathway in modulating immune response to Mycobacterium tuberculosis a bacterial pathogen and Aspergillus fumigatus an opportunistic fungal pathogen. I found that A. fumigatus-derived α-(1,3)-glucan induces maturation of DCs and secretion of various immunoregulatory cytokines that was partially dependant on Toll like receptor (TLR)-2. Analysis of CD4+ T cell polarization revealed that α-(1,3)-glucan-educated DCs induced CD4+ CD25+FoxP3+ regulatory T cell (Treg) generation that was in part dependent on the PD-L1 expression on DCs. Importantly, blocking PD-L1 on DCs enhanced IFN-γ secretion without modulating Th17 response. Similarly, M. tuberculosis induced PD-L1 dampened Th1 response without modulating Th17 response. Analysis of downstream signalling pathways indicated that, mycobacterium-responsive sonic hedgehog (SHH) mediated PD-L1 induction by inhibiting specific microRNAs, miR-324-5p and miR-338-5p that target PD-L1. Additionally, SHH induced cyclooxygenase (COX)-2 catalysed the synthesis of prostaglandin E2 (PGE2) that synergize with PD-L1 to coordinate the expansion of Tregs. My results thus demonstrate that respiratory pathogens either directly or by harbouring imuunoregulatory antigens highjack the PD-L1 pathway to suppress the protective Th1 response and orchestrate Treg generation without modulating Th17 response. Importantly, my results provide a rational for exploiting immunotherapeutic approaches that target PD-1 – PD-L1 co-stimulatory axis to restore effector T cell response to respiratory pathogens
Rui, Yuxiang. "Programmed cell death-1 inhibits inflammatory helper T cell development through controlling the innate immune response." Kyoto University, 2013. http://hdl.handle.net/2433/180613.
Повний текст джерелаKyoto University (京都大学)
0048
新制・課程博士
博士(医科学)
甲第17954号
医科博第47号
新制||医科||4(附属図書館)
30784
京都大学大学院医学研究科医科学専攻
(主査)教授 竹内 理, 教授 生田 宏一, 教授 篠原 隆司
学位規則第4条第1項該当
柴山, 史朗. "IFN-α Directly Promotes Programmed Cell Death-1 Transcription and Limits the Duration of T Cell-Mediated Immunity". 京都大学, 2011. http://hdl.handle.net/2433/147347.
Повний текст джерелаBommarito, Davide. "Inflammatory cytokines compromise programmed cell death-1 (PD-1)-mediated T cell suppression in inflammatory arthritis through up-regulation of soluble PD-1." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/inflammatory-cytokines-compromise-programmed-cell-death1-pd1mediated-t-cell-suppression-in-inflammatory-arthritis-through-upregulation-of-soluble-pd1(d4df3c4e-4af0-4eca-a29c-32b707586434).html.
Повний текст джерелаOkemo, Pauline Asami. "Regulation of plant programmed cell death by energy metabolism in the Australian resurrection grass Tripogon loliiformis." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/205617/1/Pauline_Okemo_Thesis.pdf.
Повний текст джерелаHoang, Thi My Linh. "Engineering salinity tolerance in rice by exogenous expression of cell death regulators." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/72793/1/Thi%20My%20Linh_Hoang_Thesis.pdf.
Повний текст джерелаTeo, Pei Yun. "Nucleic acid delivery using poly(ethylenimine)-based polymers for programmed death-ligand 1 (PD-L1) knockdown in ovarian cancer to enhance immunotherapy." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/39589.
Повний текст джерелаEvans, A. K. C. "The role of the programmed cell death (PD-1) pathway in the immunopathogenesis of chronic hepatitis B infection." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1138759/.
Повний текст джерелаJehn, Birgit. "The role of transcription factor AP-1 during terminal differentiation and programmed cell death of mammary epithelial cells /." [S.l.] : [s.n.], 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Повний текст джерелаGatault, Philippe. "Infection du donneur par le CMV et transplantation rénale : impact sur la réponse immunitaire spécifique et sur la survie des greffons." Thesis, Tours, 2017. http://www.theses.fr/2017TOUR3301/document.
Повний текст джерелаBackground: cytomegalovirus (CMV) is the leading cause of viral infection after solid organ transplantation. Despite a large body of literature, the effects of chronic cytomegalovirus (CMV) infection on graft outcome remain controversial.Results: we first reported that donor CMV infection (D+) was an independent risk factor of kidney graft loss, especially in pretransplant infected recipients (R+). In addition, we observed that full HLA-I mismatching was an important determinant of this risk. In a second study, we focused on effect of donor CMV infection on anti-CMV specific immune response. We reported that CMV superinfection greatly increased the number of anti-CMV IFN-ɣ-producing T cells, provided that donor and recipient shared at least one HLA-I identity. Then in D+R- HLA-A2-expressing recipients, we compared the number of anti-CMVpp65 CD8+T cells restricted by HLA-A2 depending on whether the donor expressed or not HLA-A2. Patients who received non-HLA-A2 kidneys developed very few anti-CMVpp65 T-cells restricted by HLA-A2 as compared to those who received an HLA-A2-expressing kidney. This result indicated that presentation of CMV peptides by donor cells was crucial to stimulate the expansion of pp65-specific memory CD8 T cells. Finally, we established that a SNP in the Programmed Cell Death 1 gene (PD-1.3) influenced D+ kidney and lung transplants survival, while it was also associated with the level of anti-CMV specific T-cell response. Conclusion: taken together, these data suggest that anti-CMV specific immune response is pivotal to control infection within the graft and prevent subsequent organ damages. We propose two mechanisms to explain effect of donor CMV infection on graft outcome: (1) inability of anti-CMV CD8 T cells to recognize donor-infected cells in case of full HLA-I mismatching, (2) dysfunction of anti-CMV CD8 T cells after transplantation in some patients, highlighted by our genetic study
Lema, Asqui Saúl Stalin. "Pathogen-triggered programmed cell death in plants: Metacaspase 1-dependent pathways = Muerte celular programada desencadenada por patógenos en plantas: vías dependientes de Metacaspasa 1." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/586256.
Повний текст джерелаLa respuesta hipersensible (RH) es un tipo paradigmático de muerte celular programada, que ocurre en respuesta al reconocimiento de patógenos en el sitio del intento de invasión. A pesar de más de un siglo de investigación sobre RH, muchos son los aspectos que aún se desconocen acerca de cómo está tan fuertemente regulada y cómo puede ser contenida espacialmente a solo unas pocas células. La respuesta hipersensible en Arabidopsis thaliana está controlada por la metacaspasa tipo I (AtMC1), que es un regulador positivo de la muerte celular programada desencadenada por patógenos y la autofagia, donde la regulación negativa de AtMC1 por AtLSD1 o AtMC2 puede prevenir la muerte celular incontrolada. Sin embargo, aún no está claro cómo se activa la señalización de muerte celular después de un ataque de patógenos y si existen reguladores negativos de RH adicionales para controlar la actividad del AtMC1. En nuestro laboratorio se estableció un enfoque imparcial para identificar nuevos reguladores AtMC1 basados en una purificación de inmunoafinidad de complejos que contienen AtMC1 acoplados a la espectrometría de masas. El uso de este enfoque nos ha permitido identificar nuevos reguladores de la actividad de AtMC1, en condiciones basales versus condiciones de inducción de muerte celular. En el contexto del segundo objetivo pudimos revelar que en condiciones basales AtSerpin1 actúa in vivo como un inhibidor de la muerte celular mediada por AtMC1 y del procesamiento auto-catalítico en plantas, emergiendo como un nuevo inhibidor de proteasas de muerte celular en plantas. Indicando una función conservada de un inhibidor de proteasa en reguladores de muerte celular a través de diferentes reinos. La tercera parte de este trabajo continuó con la caracterización de AtHIR2 como regulador positivo bajo condiciones inducidas de muerte celular. Nos propusimos caracterizar AtHIR2, un interactor putativo de AtMC1 recuperado de nuestro análisis de purificación de inmunoafinidad. Nuestros resultados muestran que AtMC1 co-inmunoprecipita en planta con AtHIR2, y esta interacción no depende de un sitio catalítico intacto. El fraccionamiento sub celular demuestra que esta interacción ocurre exclusivamente en la fracción microsomal, lo que indica un reclutamiento activo de AtMC1 a la membrana plasmática. Tomados en conjunto todos estos resultados, esperamos contribuir en la elucidación de la regulación de la Respuesta Hipersensible y la compleja maquinaria que permite a las células tomar decisiones vitales para la defensa contra los patógenos. Nuestros resultados contribuirán a futuros enfoques para desarrollar nuevas estrategias en la lucha contra las enfermedades de los patógenos de las plantas en los cultivos.
Marti, Andreas. "Protein kinase A, AP-1 (Fos/Jun) and the regulation of proliferation, differentiation and programmed cell death in the mouse mammary gland /." [S.l.] : [s.n.], 1995. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Повний текст джерелаTracy, Christopher M. "The Roles of Phosducin-Like Protein 1 and Programmed Cell Death Protein 5 as Molecular Co-Chaperones of the Cytosolic Chaperonin Complex." BYU ScholarsArchive, 2014. https://scholarsarchive.byu.edu/etd/5277.
Повний текст джерелаNjaci, Isaac. "The role of MicroRNAs in stress response in the resurrection plant Tripogon loliiformis." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/93740/1/Isaac_Njaci_Thesis.pdf.
Повний текст джерелаMeyerkord, Cheryl L. "The Rad9-Rad1-Hus1 complex and Bif-1 regulate multiple mechanisms that affect sensitivity to DNA damage." [Tampa, Fla.] : University of South Florida, 2009. http://digital.lib.usf.edu/?e14.2830.
Повний текст джерелаSreekanta, Suma. "Programmed cell death and induction of caspase-like protease activity in roots of Glycine max (soybean) in response to flooding stress." Miami University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=miami1218082902.
Повний текст джерелаKAUL, ANUPURNA. "Acute and Chronic Rejection: Compartmentalization and Kinetics of Counterbalancing Signals in Cardiac Transplants." Cleveland State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1418249332.
Повний текст джерелаBarbosa, Mariana de Almeida. "Plantas de cana-de-açúcar (Saccharum spp.) transformadas geneticamente com o gene AtBI-1 submetidas ao déficit hídrico em casa-de-vegetação." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/11/11144/tde-22082013-112158/.
Повний текст джерелаSugarcane is one of the main agricultural crops in the Brazilian social and economic scenario. Water stress in the culture of sugarcane is the main limiting factor for increasing productivity accounting for physiological, biochemical and molecular plants that can trigger metabolic disturbances activating programmed cell death (MCP). Knowing that the BI-1 gene has the potential to reduce the effects of MCP triggered by biotic and abiotic stresses in plants, this study aimed to analyze transgenic sugarcane that express the BI-1 gene of Arabidopsis thaliana (AtBI-1) under water stress. Also, transgenic and control plants were inoculated with Puccinia melanocephala fungus demonstrating that the genetic transformation process with the AtBI-1 gene altered the pre-existing characteristics of brown rust resistance in transgenic plants. Studies of tolerance to water deficit were performed in two experiments, the experiment 1 was prepared with transgenic and control plants with 90 days and the experiment 2 used plants with 60 days. Plants from experiment 1 were analyzed as for morphological characteristics such as number of stomata and trichomes, height and diameter of stem after plants being under water for 24 days as were analyzed photosynthetic rate, stomatal behavior, relative water content in leaves while in the experiment 2, plants were analyzed for the levels of proline, enzyme activities of guaiacol peroxidase (GPOX), ascorbate peroxidase (APX) and catalase (CAT) under water deficit for 17 days. These enzymes are involved in deactivation of active elements oxygen. The results demonstrated that the transgenic plants expressing the AtBI-1 gene presented the phenotype of lower height, higher index of leaf area, higher photosynthetic rate, higher stomatal behavior and higher relative water content in leaves than control plants increasing tolerance to drought stress. However, there were low levels of proline, low activity of GPOX activity, APX and CAT in transgenic plants during drought stress compared to control plants of the same treatment, but the observed high constitutive activity of catalase in transgenic plants. Catalase activity in these transgenic plants suggests the possibility of interaction between AtBI-1 and calmudolinas. Future studies may contribute to understand whether the BI-1protein is essential for the activation of catalase by calmudolinas.
Peththa, Thanthrige Nipuni. "Dissecting the molecular mechanisms of AtBAG4-mediated stress tolerance." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/235369/1/Nipuni%2BPeththa%2BThanthrige%2BThesis%283%29.pdf.
Повний текст джерелаPatah, Poliana Alves. "Análise do perfil imunofenotípico das células NK e sua correlação com a expressão de PD-1 e PD-L1 em indivíduos infectados pelo HIV." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-06022017-152423/.
Повний текст джерелаThe expansion of our knowledge about the HIV and its effects on the entire immune system has led the development of a vast therapeutic arsenal. Survival for newly diagnosed cases is now measured in decades;? some patients, however, never recover full immune function following the initial aggression inflicted by HIV, despite adequate treatment. NK cells are identified as innate immunity components, responsible for fighting viral infections and tumors. They are separated in CD56dim and CD56hi cells, which present different cytotoxicity and cytokine production capacity. A third distinct subpopulation constituted by CD56neg cells can be found in minimal counts in healthy adults, but is present in newborns and is expanded in chronically HIV- infected subjects;? these cells can be identified as CD7+CD16+. Among others, NK cells express activating and inhibitory receptors called KIR, which interact with HLA molecules and identify \"self\" cells and cells that have downregulated its expression as an immunologic evasion strategy. Studies have documented the importance of KIR and HLA interaction in HIV/AIDS infection clinical course, particularly involving the receptor KIR3DL1. PD-1 is an immune checkpoint that can be upregulated by tumors and chronic viral infections. PD- 1 expression on T cells is correlated to prognostic factors in HIV/AIDS infection; NK cells have been shown to express it, but further information is necessary. This study aimed at investigating PD-1 and its ligand PD-L1 expression on NK and monocytes in HIV-infected participants and controls. We recruited a group of participants who were diagnosed during acute phase of HIV infection and have been followed ever since, a group of participants who were diagnosed after unknown interval since seroconversion, and a group of uninfected controls who have a high risk due to sexual exposure. Samples were freshly processed at LIM-60; PD-1 and other markers were analyzed by multicolor flow cytometry. We found PD-1 expression on NK cells was correlated to T CD4+ cell counts and PD-1 expression on T cells, in infected participants; among them, participants followed since acute infection expressed less PD-1. They also expressed less PD-L1 in monocytes, as compared to participants diagnosed after unknown interval since seroconversion, as well as compared to the uninfected group. We found significant increase in proportion of KIR3DL1-expressing cells among CD56neg cells in infected participants compared to the uninfected group. We concluded that PD-1 expression on NK cells is increased in people infected by HIV and correlated to other immunologic parameters such as T CD4+ counts and PD-1 expression on T cells. NK cell exhaustion may, therefore, contribute to the immune damage induced by HIV-1 infection and can be also explored as a target to find new ways to restore antiviral immunity
Ullah, Matti. "Immune Checkpoints in Peritoneal Carcinomatosis : HLA-G, PD-L1 & the Impact of Cancer Therapies." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS288.
Повний текст джерелаPeritoneal carcinomatosis (PC) is a term used for widespread metastatic dissemination of cancer to the peritoneal cavity. It is characterized by the accumulation of fluid called “ascites” and is considered a terminal stage of cancer, as it is hard to treat. The overall survival rate for untreated patients is six-months. However, owing to modern techniques like HIPEC, the survival rate can be increased up to five years. The ascites accumulated in PC, consists of tumor cells, cytokines and immune cells. Cancer cells express specific proteins to suppress immune cells activity and their attack, known as immune checkpoints. PD-1/PD-L1 and CTLA-4 are well established immune checkpoint pathways adapted by cancer in evading immunity. Recently, HLA-G has been recognized as an immune checkpoint and has been found to decrease overall survival in several types of solid cancers. We evaluated the expression of HLA-G in ascites from ovarian carcinomatosis. We found that HLA-G is expressed by cancer cells in ascites from all of the patients(n=16) with ovarian carcinomatosis. Moreover, increased levels of sHLA-G1 and HLA-G5 were found in ascites. This presence of sHLA-G isoforms was found to be positively correlated with Tregs and negatively correlated with cytotoxic T-cells (CD8) and NK-cells suggesting the role of HLA-G in immune suppression. Further, we found that ascites can induce the expression of HLA-G in “Hospicells” via inflammatory cytokines. Among the inflammatory cytokines, TGF-β and IL-1β are of crucial importance in HLA-G induction with IL-1β being more potent compared to TGF-β. Further, we found that IL-1β induces HLA-G expression through NF-κB pathway.In a separate cohort of peritoneal carcinomatosis(n=27), consisting of patients with cancer from a different origin, we found that cancer cell cluster in ascites (n=23) had a heterogeneous gene expression of PD-L1, CTLA-4 and HLA-G. Further, we found that all of the patients presented soluble levels of HLA-G in their ascites. However, one patient was negative for soluble PD-L1 and only 5 patients presented soluble CTLA-4 levels in their ascites. This heterogeneity explains why some of the patients respond to immune therapy while others don’t. This also suggests the need for prescreening patients before immune therapy. Moreover, we found a very strong positive correlation (rs=0.793) between gene level of PD-L1 and CTLA-4, while no correlation was found for HLA-G with PD-L1 and CTLA-4 suggesting that HLA-G acts independently of both the immune checkpoints. Also, we evaluated the expression of these immune checkpoints by cells in peritoneal tissue (n=20). We found low expression of HLA-G and PD-L1, but the majority of the samples were found strongly positive for sHLA-G presence. This sHLA-G can provide an immune-suppressive environment for the attachment of the cancer cell clusters to the peritoneal membrane to form cancer nodule. Additionally, we developed an in-vitro cytotoxicity assay to show that the ascites can provide the immune-suppressive action by interfering with immune cell interaction and delaying the lysis of cancer cells by the immune cells.In parallel, we found that the differentiation of the cancer cells results in increased expression of immune checkpoints like HLA-G or PD-L1. This may render these cells more immune resistant and can protect against immune attack. However, in-vivo mice model is needed to study the oncogenic potential of these differentiated cells. Further, we report that the expression of HLA-G and PD-L1 is dependent on the cell cycle phase. The cancer cells, if blocked in mitotic phase express high levels of HLA-G and PD-L1, while lowest expression was observed in G1-phase. Therefore, we suggest avoiding the use of mitotic inhibitors as it may increase the immune suppression of cancer. Moreover, as Ki-67 is directly related to the mitotic index, we suggest developing a Ki-67 scale to evaluate the immune-suppressive profile of cancer patients
Niestegge, Julia Klara [Verfasser], Inge [Gutachter] Bauer, and Hug [Gutachter] Aubin. "Das Expressionsmuster der MicroRNA-1 und -21 und des Tumorsuppressorgens Programmed Cell Death 4 bei der anästhetischen Präkonditionierung mit Isofluran. - Molekularbiologische Untersuchung im Myokard der Ratte im Rahmen einer in vivo-Studie zum kardioprotektiven Effekt von Isofluran und den zugrunde liegenden Mechanismen - / Julia Klara Niestegge ; Gutachter: Inge Bauer, Hug Aubin." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1179448162/34.
Повний текст джерелаMelotto-Passarin, Danila Montewka. "Transformação genética de cana-de-açúcar por biolística e Agrobacterium tumefaciens visando estudar o mecanismo de morte celular programada." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/11/11144/tde-14042009-082016/.
Повний текст джерелаSugarcane is one of the main crops planted in Brazil and presents significant socioeconomic and agribusiness importance to the country. The world scene is quite favorable as regards the marketing of its two main products, sugar and alcohol, driving the development of the national sugar-alcohol sector. Therefore, the sugarcane genetic breeding appears as the fundamental base for developing new varieties for the maintenance and increase of agribusiness in the sugarcane agroindustry. Genetic engineering techniques, such as the nuclear genetic transformation, are providing excellent results in genetic breeding of this crop allowing reducing the cost and time to obtain new varieties. Based on the importance of obtaining varieties tolerant to different biotic and abiotic stresses that induce metabolic disturbances and activate the process of programmed cell death, this work aimed to transform sugarcane variety RB835089 with the cDNA of AtBI-1 gene, isolated from Arabidopsis thaliana, to suppress the induction of the cell death mechanism under stress condition. For this, embryogenic calli were used as target explant, by using two methods of transformation, the cotransformation by biolistic, and mediated by Agrobacterium tumefaciens in which two techniques were tested: (a) direct inoculation of calli in bacterial suspension; (b) agrobiolistic which is the bombardment of calli with tungstein particles followed by inoculation in bacterial suspension. The AtBI-1 protein (Bax inhibitor-1) presents homologs in other organisms and is located in the endoplasmic reticulum membranes. It has cytoprotective functions by modulating the mechanism of programmed cell death induced by biotic and abiotic stresses. As results of this work, different efficiency rates in genetic transformation were obtained in the method mediated by A. tumefaciens in the two techniques tested, and that their rates were higher than those achieved using the cotransformation by biolistic. The heterologous expression of cDNA of AtBI-1 gene in sugarcane attenuated the induction of cell death pathways in the presence of tunicamycin antibiotic, an inducer of stress in the endoplasmic reticulum, being proven by the increased stress tolerance of transgenic plants compared with sugarcane wild type that were affected in the root growth, total chlorophyll content, showing typical symptoms of programmed cell death such as leaf chlorosis and irregular morphology of the roots, with subsequent death of the root system.
Muszak, Damian. "Synthesis and characterization of small-molecule inhibitors that target the programmed cell death ligand 1 protein." Praca doktorska, 2020. https://ruj.uj.edu.pl/xmlui/handle/item/276404.
Повний текст джерелаThe main hope of modern medicine is the development of effective cancer treatments. A common cause of cancer occurrence is the deactivation of the immune system through blockade of intercellular communication pathways. Diseased cells are not recognized properly, and thus cannot be neutralized and removed from the organism. One of the factors responsible for inhibiting T-cells activity is the programmed cell death protein 1 receptor (PD-1), located on the surface of immune cells. Interaction of PD-1 with its natural ligand PD-L1 (programmed cell death ligand 1) causes T-cells deactivation. PD-L1 overexpression is found in many cancers like, for example, lung cancer, bladder cancer, and melanoma. Blockade of the PD-1/PD-L1 interaction has become the basis of cancer immunotherapy based on monoclonal antibodies (mAbs), which has been spectacularly successful in the treatment of several cancers. Six of the clinically tested antibodies have now been approved by the US Food and Drug Administration (FDA) and are currently used in immune oncology. The antibody-based therapy has however several disadvantages. The cost of treatment is high because of antibodies production methodology; additionally, their storage conditions are strict. The mAbs, in general, are characterized by low tumor penetration and poor control of pharmacokinetics and thus mAb-related toxicity (e.g., immune-related adverse effects, irAEs). It is expected that the development of small-molecular inhibitors for the PD-1/PD-L1 interaction could solve some of these problems by providing the increased ability for tumor penetration, lower production costs, reduction of side effects during treatment, and oral administration. The aim of this doctoral dissertation was the synthesis of small-molecule inhibitors that target the PD-1/PD-L1 interaction. These inhibitors are based on the N-(4-(dimethylamino)benzyl)-N-methylacetamide, 1-indanole, N-phenyl-δ-valerolactam, N-biphenyl-δ-valerolactam and 2'-methyl-m-terphenyl scaffolds, designed through structure analysis of the known PD-L1 inhibitors reported in the literature. The small molecules designed this way were successfully synthesized, using linear and/or partially convergent syntheses. The activities of the compounds were assessed with the Homogeneous Time-Resolved Fluorescence (HTRF) assay. These studies showed that only the terphenyl-based inhibitors were characterized by high potency to inhibit the PD-1/PD-L1 interaction. In further research, the structure of the terphenyl core was optimized by synthesizing a group of derivatives whose activity was evaluated after each modification. Final optimization led to the small molecules characterized by high binding affinities to the PD-L1 protein, with IC50 values in low-nanomolar ranges. The potency of the compounds to activate T-cells was also assessed in the in-vitro cell-line assay. Six of the final compounds induced the T-cells activation with the EC50 values in the range from 1.03 to 11.08 μM. The PD-L1 binding mode of the final optimized terphenyl small-molecules was examined by 1H nuclear magnetic resonance (NMR) spectroscopy. The NMR spectra indicated that all terphenyl-based compounds initiate protein oligomerization whereas dimer formation was shown by X-ray crystallography. The X-ray structural studies revealed the small molecule located at the center of the homodimer, filling a deep hydrophobic channel between the interfaces of two PD-L1 molecules. This structural information can be useful in further structure optimization of the terphenyl-based scaffolds.
Hu, Shu-Wei, and 胡書瑋. "Role of phthalate plasticizer in the regulation of Programmed death-ligand 1 (PD-L1) expression in breast cancer cells." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/yma3g6.
Повний текст джерелаWang, Chia-Jen, and 王嘉嫃. "Protective role of transgenic programmed death 1 ligand 1 and ligand 2 in autoimmune diabetic mice." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/85657608279041508004.
Повний текст джерела國防醫學院
生命科學研究所
96
Coinhibitory signal mediated via programmed death 1 (PD-1) plays a critical role in down-regulating immune responses and maintaining peripheral tolerance. Since PD-1 provides the negative signaling upon interaction with its ligands, PD-L1 or PD-L2, we generated the transgenic NOD mice overexpressing PD-L1 or PD-L2 in pancreatic cells to see whether the “additional” inhibitory signal provided by transgenic PD-L1 or PD-L2 can protect mice from autoimmune diabetes. Our results indicated that both transgenic lines displayed an islet-specific expression of PD-L1 or PD-L2 transgene, respectively. The spontaneous diabetic incidences were markedly decreased both in PD-L1 and PD-L2 transgenic mice, although the PD-L1 transgene provided better protection than did PD-L2. To investigate whether the protective mechanism works through down-regulation of diabetogenic T cells, we performed an adoptive transfer experiment in the NOD/SCID system. NOD/SCID mice receiving lymphocytes from PD-L1 or PD-L2 transgenic mice became diabetic with slower kinetics compared to mice receiving lymphocytes from their non-transgenic controls. Moreover, lymphocytes collected from NOD/SCID recipients that previous receiving lymphocytes from PD-L1 or PD-L2 transgenic mice revealed less proliferative potential than lymphocytes obtained from recipients that previous receiving lymphocytes from control mice. Islets in diabetic recipients that received lymphocytes from PD-L1 transgenic mice survived moderately longer than control islets. We illustrate the modulatory roles of PD-L1 and PD-L2 in down-regulating diabetogenic T cells in NOD mice. In summary, our results demonstrate that enhancing PD-1 signaling by the presence of either transgenic PD-1 ligands provides beneficial immune modulation in autoimmune diabetes.
Chieh-HaoLi and 李介豪. "Development of Programmed Death-ligand 1 Targeting Aptamers by Nanodisc-based SELEX." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/wuzy4q.
Повний текст джерелаGalvan, Veronica. "A study on herpes simplex virus 1 infection and programmed cell death /." 1999. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:9951785.
Повний текст джерелаWei-Chun, Wang. "Genetic Analysis of C. elegans dapk-1 in the Programmed Cell Death Process." 2006. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2007200616102000.
Повний текст джерелаWang, Wei-Chun, and 王維君. "Genetic Analysis of C. elegans dapk-1 in the Programmed Cell Death Process." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/32909847085980584773.
Повний текст джерела國立臺灣大學
分子與細胞生物學研究所
94
Programmed cell death (apoptosis) is a biological process essential for the development and homeostatic maintenance of multicellular organisms. The main genetic pathway of apoptosis governed by the genes egl-1, ced-9, ced-4, and ced-3 has been characterized in the nematode Caenorhabditis elegans and shown to be highly conserved through evolution. DAPK-1, an ortholog of human DAPK, was previously found to be a positive mediator of somatic programmed cell death in our lab. Here we analyzed dapk-1 mutants (gk219, ju4, ju469, and ju557) in detail. These mutants all exhibited reduced numbers of cell corpses generated by cell death with an allelic order: ju557 (strongest), ju469, gk219, and ju4 (weakest). ju557 was a dominant allele, while ju469 was recessive. Furthermore, the embryonic cell death of these mutants was sensitive to temperature alternation. In addition, dapk-1 mutants (gk219 and ju469) also had reduced numbers of germline cell corpses. To position dapk-1 in the genetic pathway, we expressed egl-1 ectopically in the touch neurons in different dapk-1 (gk219 and ju469) mutant backgrounds. We found that gk219 suppressed but ju469 augmented the cell-killing activity caused by egl-1overexpression. A similar result was obtained when ced-4 was overexpressed in the touch neurons in these mutants. Co-expression of dapk-1 in these cells recovered egl-1 induced cell death in gk219, suggesting that DAPK-1 functioned autonomously to promote cell death. Antibodies against DAPK-1 were generated to examine its expression pattern. DAPK-1 was widely expressed during embryogenesis. The protein exhibited a filamentous pattern in the cytoplasm and was enriched near the membrane periphery. Conclusively, DAPK-1 participates in both embryonic and germline cell death and localizes in the cytoplasm in embryonic cells. It is also indicated that this protein may play different roles depending on the cellular subset.
Hanley, Ronan. "Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries." Thesis, 2017. https://dspace.library.uvic.ca//handle/1828/9136.
Повний текст джерелаGraduate
2019-02-15
Yang, Ching-Yao, and 楊景堯. "Programmed Death-Ligand 1 Expression in Lung Cancer and its Association with Clinicopathological Characteristics, Tumor Microenvironments, Driver Mutations, and Clinical Outcomes." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/dv2xp2.
Повний текст джерела國立臺灣大學
病理學研究所
106
Lung cancer is the leading cause of cancer-related death worldwide despite a lot of advances in cancer treatment have been achieved in recent decades. Currently, the treatment strategy for advanced lung cancer has been moved forward from conventional platinum based chemotherapy, molecular target therapy, to the era of immunotherapy. Immune checkpoint inhibitors are now the most promising immunotherapy which can unleash the immunosuppression cancer cell posed on host immune system. Among the various immune checkpoints, programmed-death 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) are the most predominating ones which are found in lung cancer and many other types of neoplasms. Expression of PD-L1 on cancer cells can deliver an inhibitory signal through PD-1 on T cells to down-regulate the activity of T cells and prompt cancer escape from host immune systems. Therefore, the expression pattern of PD-L1 on cancer cells becomes an important issue, either for recognition of tumor-host immune balance, or for potential prediction of anti-PD-1/PD-L1 immunotherapy. We conducted serial studies to examine tumor PD-L1 expression in two stage I cohorts of non-small cell lung cancer (NSCLC). The first one is an adenocarcinoma cohort consisting of 163 patients. Using ≥ 5% membranous positive staining cells as cutoff value, we found PD-L1 expression was positive in 65 of 163 patients (39.9%). Higher grade of differentiation and vascular invasion were associated with PD-L1 expression. The multi-variate analysis for survival showed PD-L1 expression was an independent good prognostic factor of disease free survival (DFS), while higher grade of differentiation and abnormal carcinoembryonic antigen (CEA) were poor prognostic factors. The only favorable and independent prognostic factor for overall survival was earlier stage (IA vs IB). In the subsequent study, we conducted a deeper and thorough evaluation of PD-L1 expression in another cohort of stage I squamous cell carcinoma (SqCC) (n=105). Because tumor microenvironments are quite crucial for immune-oncology, we analyzed the composition of tumor infiltrating lymphocytes (TIL) in addition to tumor cell PD-L1 expression and clinicopathological features. Using the same cutoff value of 5%, we found that PD-L1 expression was positive 59 of 105 patients (56.2%), which was more prevalent than the ADC cohort (SqCC vs ADC, 56.2% vs 39.9%, p<0.001). The exploration of TIL composition showed that PD-L1 expression positively correlated with tumor epithelial CD8+ T cell and tumor stromal CD4+ T cell infiltration, and negatively correlated with PD-L1+ immune cells infiltrations in tumor stroma. For the individual TIL, tumor epithelial CD8+ T cell and tumor stromal CD4+ T cell infiltrations were associated with a better DFS and OS; while tumor stromal regulatory T cells infiltrations were associated with a poor DFS and OS. By multivariate analysis, PD-L1 and tumor stromal CD4+ T cell infiltrations were independent prognostic factors of OS but only had a trend toward better DFS. Our results may suggest that in early stage NSCLC, PD-L1 expression reflects a phenomenon of adaptive resistance that an effective host immunity may still exist and is powerful enough to force cancer cell develop an escape mechanism, especially by expressing PD-L1. However, the existence of PD-L1 expression in early stage lung cancer may not point to a status of successful immune escape. We hope our serial studies may help the delineation of cancer immunology and tumor microenvironment of NSCLC.
Chen, Shu-Ching. "Molecular Mechanisms of P-selectin Glycoprotein Ligand-1-Mediated Cell Death in Activated T Cells." 2004. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-3007200411155800.
Повний текст джерелаChen, Shu-Ching, and 陳淑靜. "Molecular Mechanisms of P-selectin Glycoprotein Ligand-1-Mediated Cell Death in Activated T Cells." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/96496849285003064251.
Повний текст джерела國立臺灣大學
免疫學研究所
92
Abstract The immune system evolves several sophisticated strategies to regulate immune responses. In general, contact with their specific antigen causes naïve T cells to proliferate and differentiate into effector cells. After the pathogen is destroyed, most effector T cells are eliminated, thereby preserving the size of T cell repertoire. During each stage of this process, the fate of life or death of T cells is strictly regulated. For many years, the importance of death receptors such as Fas and other TNF receptor family members as well as depiction of death signaling pathway have been emphasized in regulation of activated T cells. In recent years, however, increasing evidence has shown that molecules other than death receptors can also trigger T-cell death. Inhibition of classical caspases can not always prevent T cell death. These observations indicate that death signaling in activated T cells is regulated in a very complicated way. In order to address the death mechanisms of activated T cells, panels of hamster monoclonal antibodies against mouse activated T cells were generated in our laboratory. Those antibodies with death-triggering function on mouse activated T cells were screened. The most significant one, named TAB4, was found to recognize P-selectin glycoprotein ligand-1 (PSGL-1) or CD162. PSGL-1 is well known for mediating leukocyte trafficking by interaction with selectins during inflammatory responses. Using the anti-PSGL-1 monoclonal antibody, TAB4, here we demonstrate for the first time that cross-linking of PSGL-1 can trigger a death signal in activated T cells. In contrast to classical cell death, PSGL-1-mediated T cell death is caspase-independent. It involves translocation of apoptosis-inducing factor from mitochondria to nucleus as well as mitochondrial cytochrome c release. Ultrastructurally, both peripheral condensation of chromatin and apoptotic body were observed in PSGL-1-mediated T-cell death. In present study, immobilized P- or E- selectin is also demonstrate to have death-triggering effect on activated T cells. Collectively, this study demonstrates a novel role of PSGL-1 in controlling activated T-cell death and thus advances our understanding of immune regulation. Our intent in this study is to clarify the molecular mechanisms that determine death of activated T cells and to indicate how these can be integrated into a more complete description of the T cell homeostasis.
Bootwala, Ali Habib. "L2pB1 cells are essential for the inhibition of 3D tumor spheroids by syngeneic peritoneal immune cells." Thesis, 2019. https://hdl.handle.net/2144/34840.
Повний текст джерелаLi-ChanChang and 張立展. "Interaction between secreted protein acidic and rich in cysteine (SPARC) and programmed death ligand 1 (PD-L1) promotes EMT program via WNK1 activation in lung adenocarcinoma." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/3x6kh3.
Повний текст джерела李讚虔. "1.The causes of drastic decrease in algal group of Codium edule in Kenting by the photosynthetic and morphological approaches 2.The morphology of the programmed cell death on Chlorella pyrenoidosa after heat stress." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/43462206757811116257.
Повний текст джерела國立清華大學
生物資訊與結構生物研究所
93
PartI The growth period for many macroalgae in Ken Ting is from March to June. According to preview studies, Codium edule has the largest covering ratio on the coral reef among all the macroalgae, but its population above 5m depth of subtidal drastically decreases from July to September. After November C. edule gradually recover and rapid growth state until March next year. In this article, we use the chlorophyll fluorescence and transmission electrons microscopic(TEM) to find out the possible reasons for C. edule drastically decrease between July to September. According to chlorophyll fluorescence studies, we found that C. edule lost photosynthetic circadian rhythm at 33℃, but it was not lethal at the temperature. Upon exposure to 35℃, the photosynthetic activity of the algae would drastically decrease after 4 hours and drop to zero after 8 hours. From TEM studies, the vacuoles reduce in size which was accompanied by the appearance of many small vesicles after exposing to 35℃ about 4 hours. In the meantime, the algae became soft and underwent plasmolysis that is believed a key induced cell death. Finally, the vacuole collapsed completely and the plasmamembrane destroyed which means the algal cells started to necroses. In summery, our data suggested that 35℃ would cause the vacuole to collapse and lead to C. edule is cell death. This might be for the reason it drastically decrease between July to September. PartII In this study, we examined the programmed cell death (PCD)of synchronous Chlorella pyrenoidosa culture by transmission electron microscopic(TEM). The PCD started right affect high temperature stress(46.5℃)followed by continuous illumination under normal culture condition. We noticed that high temperature stress induced chromatin condensation around the inner membrane of nuclear and something in vacuole. These phenomena elucidated the immediate effect on Chlorella brought about by heat stress. In 6 h after stress we found that Chlorella cell were bleached. But according to the images of TEM, the destruction of the thylakoids started at 8 h but not at 6 h. The direction of thylakoid destruction was from inner to outer side of Chlorella cells. At the same time, the structures of vacuole, mitochondria and nuclei in Chlorella also disappeared. These showed that there were dramatic morphological changes in Chlorella between 6-8h. The disappearances of organells were followed by and then the cytosolic condensation which in turn induced plasmolysis, but the later phenomenon would vanished gradually. In addition, the chromatins condensation formed an annular structure that was preserved for more than two days. In summery, Chlorella would die after heat treatment. The death was induced by a spontaneous mechanism and a programmed process different from ordinary.
Mathieu, Mélissa. "Étude de la différenciation des lymphocytes T CD8+ effecteurs et mémoires : rôle de la cellule présentatrice d’antigène et de la voie de signalisation Notch." Thèse, 2014. http://hdl.handle.net/1866/11791.
Повний текст джерелаFollowing an infection with a pathogen, antigen-specific naive CD8+ T lymphocytes (Tn) will proliferate and differentiate into effector (Te) cells. Those Te cells will produce different cytokines and acquire a cytotoxic activity, leading to pathogen clearance. Only 5 to 10 % of Te cells will survive and differentiate into memory CD8+ T lymphocytes (Tm) able to respond rapidly following a second encounter with the same pathogen, contributing to the success of vaccination. However, the mechanisms regulating Te and Tm cells development remain incompletely understood. To better understand the signals required for CD8+ T lymphocytes during an immune response, we proposed two hypotheses. First, we propose that different antigen presenting cells (APCs) can deliver different signals to CD8+ T lymphocytes at the time of priming leading to different outcome. Given their potential for use in immunotherapy, we compared the ability of CD40 activated B lymphocytes (CD40-B) and dendritic cells (DCs) to activate CD8+ T lymphocytes. We have shown that CD40-B cell immunisation leads to an effector response but very few Tm cells are generated compared to DC immunisation. The Te cells generated following CD40-B cell immunisation are functional because they secrete cytokine, are cytotoxic and control a Listeria monocytogenes (Lm) infection. We propose that CD40-B cells secrete less cytokines and interact during shorter period of time with the CD8+ T lymphocytes, without engulfment, contributing to the decreased Tm generation observed following immunisation with CD40-B cells. Second, among the signals provided by APC at the time of CD8+ T lymphocyte priming, we have hypothesised that the Notch signalling pathway influences Te and Tm cell differentiation by inducing a particular genetic program. Using an in vitro system, we first studied the role of the Notch signalling pathway in the hours following CD8+ T lymphocyte priming. We demonstrated that Notch signalling directly regulates PD-1 expression. Then, studying mice where Notch1 and Notch2 receptor genes are deleted only in mature CD8+ T lymphocytes, we characterised the role of the Notch signalling pathway on Te and Tm differentiation during an immune response. Our results show that following Lm infection or a DC immunisation, the Notch signalling pathway promotes the differentiation of short lived effector cells Te cells (KLRG1highCD127low) meant to die by apoptosis. However, the Notch signalling pathway did not influence the generation of CD8+ Tm cells. Most interestingly, IFN- regulation by the Notch signalling pathway depends on the activation context. Indeed, following Lm infection, lack of Notch receptors does not impact IFN- secretion by Te cells while it is significantly decreased following a DC immunisation suggesting a context dependant role for the Notch signalling pathway. Our findings provide a better understanding of the key signals provided by APC as well as the Notch signalling pathway, and thus the molecular mechanisms leading to CD8+ lymphocyte effector and memory generation which is crucial as this knowledge may ultimately lead to improved vaccination.