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1

Jaswani, Tamika S., Meeta Desai, Douglas Grider und Jonathan M. Bern. „Immune Check Point Inhibitor-induced Colitis“. American Journal of Gastroenterology 112 (Oktober 2017): S858—S860. http://dx.doi.org/10.14309/00000434-201710001-01575.

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2

Bobart, Shane A., Itunu Owoyemi, Joseph Grande, Nelson Leung und Sandra M. Herrmann. „Immune Check Point Inhibitor–Associated Endothelialitis“. Kidney International Reports 5, Nr. 8 (August 2020): 1371–74. http://dx.doi.org/10.1016/j.ekir.2020.05.027.

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3

Ashour, Tarek, Georges Nakhoul, Pradnya Patil, Pauline Funchain und Leal Herlitz. „Immune Check Point Inhibitor–Associated Glomerulonephritis“. Kidney International Reports 4, Nr. 2 (Februar 2019): 355–59. http://dx.doi.org/10.1016/j.ekir.2018.10.017.

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4

Kumar, Aswini, Maximilian Lee und Talhat Azemi. „IMMUNE CHECK POINT INHIBITOR MYOCARDITIS MIMICKING ACS“. Journal of the American College of Cardiology 73, Nr. 9 (März 2019): 2681. http://dx.doi.org/10.1016/s0735-1097(19)33287-5.

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5

Nilajgi, Shalini, Nicholas Kasmeridis und Kichendasse Ganessan. „A Case Of Immune Check Point Inhibitor - Induced Hypophysitis“. Journal of the Endocrine Society 5, Supplement_1 (01.05.2021): A560. http://dx.doi.org/10.1210/jendso/bvab048.1142.

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6

Suchý, David. „Immune-related adverse events associated with immune check-point inhibitors“. Klinická farmakologie a farmacie 33, Nr. 3 (28.10.2019): 20–24. http://dx.doi.org/10.36290/far.2019.019.

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7

Marthey, Lysiane, Raef Abdallah, Christophe Bellanger, Clément Bresteau, Antoine Meyer, Aurélien Amiot und Franck Carbonnel. „Immune check-point inhibitors related enterocolitis“. Hépato-Gastro & Oncologie Digestive 30, Nr. 8 (Oktober 2023): 826–32. http://dx.doi.org/10.1684/hpg.2023.2641.

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8

Johncilla, Melanie, Shilpa Grover, Xuchen Zhang, Dhanpat Jain und Amitabh Srivastava. „Morphological spectrum of immune check‐point inhibitor therapy‐associated gastritis“. Histopathology 76, Nr. 4 (18.02.2020): 531–39. http://dx.doi.org/10.1111/his.14029.

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9

Kim, Jin Young, Chi Heum Cho und Hong Suk Song. „Targeted therapy of ovarian cancer including immune check point inhibitor“. Korean Journal of Internal Medicine 32, Nr. 5 (01.09.2017): 798–804. http://dx.doi.org/10.3904/kjim.2017.008.

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10

Vergne-Santiago, Norma, Ernesto Jos E. Sola Sanchez und Michelle Marie Mangual Garcia. „Immune Check Point Inhibitors Triggering Non Autoimmune Polyendocrinopathy“. Journal of the Endocrine Society 5, Supplement_1 (01.05.2021): A136—A137. http://dx.doi.org/10.1210/jendso/bvab048.275.

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Abstract The superlative therapeutic response of cancer immunotherapy is activation of the immune system against cancer cells. Currently, one of the most considered immune system enhancer are the immunomodulatory antibodies well known as checkpoint inhibitor therapy. Among this type of treatment, programed cell death-1 receptor blocker, is one of the most sought-after therapies on demand now a day. Notwithstanding the important clinical benefits of this therapeutic modality, serial autoimmune adverse effects and variety of atypical presentations of life-threatening endocrinopathies are expected to occur. We present a case of a 78-year-old man with dyslipidemia and lung CA who was referred to our clinic after developing electrolyte disturbances with associated dizziness and fatigue one month after Pembrolizumab therapy initiation. Physical exam was unremarkable. Laboratory data was consistent with mild hyponatremia, hyperkalemia and adequate fasting blood sugar levels. Aldosterone levels were extremely low, ACTH levels were extremely high with inappropriate low total cortisol response and negative 21-Hydroxylase antibodies. Diagnosis of primary adrenal insufficiency was established and Fludrocortisone 0.05 mg PO daily therapy was started with further resolution of hyponatremia and initial symptoms. In addition, concurrent primary hyperthyroidism along with thyroid RAIU-Scan results were consistent with thyroiditis, but TSI and TPO’s antibody levels were unexpectedly negative. Eventually, a suspicious thyroid nodule was identified requiring biopsy. Initial FNA results showed a follicular lesion of undetermined significance followed by a benign finding when repeated after six months. During follow up, patient’s primary hyperthyroidism converted to severe primary hypothyroidism without any intervention for her prior hyperthyroidism. Patient’s TPO’s levels remain undetectable and his current status is post-thyroiditis with residual primary hypothyroidism. Primary adrenal insufficiency also persist and its antibodies have not yet been identified either. It is known that autoimmunity can predispose to the development of primary adrenal and thyroid disorders in patients undergoing PD-1 receptor blockers therapy against cancer. Both disorders are increasingly recognized and reported as one of the most common adverse effects presenting in patients treated with these agents. However, to our knowledge, cases of non-immune related adverse effects are barely documented. This case of uncommon endocrine manifestations related to checkpoint inhibitors therapy is meritorious of being reported since it should raise awareness in the medical community for prompt identification of signs and symptoms, as well as to offer adequate management, accurate treatment and provide a better standard of care.
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11

Korotaeva, A. A., N. V. Apanovich, E. A. Braga, V. B. Matveev und A. V. Karpukhin. „Current advances in kidney cancer immunotherapy“. Cancer Urology 15, Nr. 4 (16.01.2020): 30–38. http://dx.doi.org/10.17650/1726-9776-2019-15-4-30-38.

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In Russia, among tumors of the genitourinary system, renal cell carcinoma takes the 2nd place after prostate cancer. In 25 % of patients at the time of diagnosis, metastases are detected. Treatment of advanced stages of renal cell carcinoma is often not effective enough. The introduction into clinical practice of modern immunotherapeutic drugs based on inhibition of immune check points has changed the prognosis of the disease for many patients with various malignant neoplasms, including kidney cancer. In this article, we described the results of recent clinical trials on the use of immunotherapy in the treatment of kidney cancer. The most effective is combination of drugs that inhibit different immune check points, and a combination of a check point inhibitor with a targeted drug. This approach is likely to be a major one in the treatment of renal cell carcinoma in the short term. Combinations of control point inhibitors with radiation therapy and immunomodulatory drugs, the role of miRNAs in the regulation of expression of immune control points, the significance and characteristics of the microbiome in connection with the success of immunotherapy for kidney cancer, gene expression profiles as biomarkers of the immune response, and other biomarkers are considered. A better understanding of the mechanisms that limit the effectiveness of immune control point inhibitors will improve future treatment.
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12

Master, Samip R., Arelis Robinson, Glenn Morris Mills und Richard P. Mansour. „Cardiovascular complications of immune checkpoint inhibitor therapy.“ Journal of Clinical Oncology 37, Nr. 15_suppl (20.05.2019): 2568. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.2568.

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2568 Background: Cardiac toxicity has largely been underestimated toxicity of checkpoint inhibitors. There have been several cases of myocarditis and fatal heart failure reported in patients treated with checkpoint inhibitors. We did a retrospective analysis of data of adverse effects of drugs that has been made available to public by the FDA. Methods: The FDA has made the data on adverse effects of various treatments available to general public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the cardiac toxicities of various immune check point inhibitor therapies available at FDERS for the years 2017-2018. Results: The reviewed the reported side effects of pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab and ipilimumab from FDA data. A total of 36,848 toxicities from immunotherapies were reported. Out of that, 2316(6.2 %) were cardio toxicities and 816 were fatal. The most common cardiac complications were as follows: myocarditis (15%), atrial fibrillation (13%), pericardial disease including pericardial effusion (13%), cardiac failure (17%) and coronary artery disease (19%). Approximately 50%, 43%, 40% 22% and 15 % of cases with myocarditis, ischemic heart disease, cardiac failure, atrial fibrillation and pericardia disease were fatal. Conclusions: Out of the reported cases of adverse reaction to check point inhibitor, 6.2% were cardio toxicities. 35% of cardio toxicities were fatal. Half of the cases who developed myocarditis died. There was no statistical difference in rate of cardiotoxicities caused by PD1, PDL1 or CTLA 4 inhibitors.
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13

Durno, Carol A., Melyssa Aronson, Melissa Edwards, Simon Ling, Valérie Larouche, Annika Bronsema, Michael Osborn et al. „Immune Check Point Inhibitor Treatment for Young Patients with Hypermutant Cancers“. Gastroenterology 152, Nr. 5 (April 2017): S141. http://dx.doi.org/10.1016/s0016-5085(17)30801-6.

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14

Albert, Stewart, Gouyu Ling, Srikanth Nadella und Aparna Yeggalam. „ODP170 Check Point Inhibitor Associated Multi-Endocrine Dysfunction Presenting With Euglycemic Ketoacidosis“. Journal of the Endocrine Society 6, Supplement_1 (01.11.2022): A71—A72. http://dx.doi.org/10.1210/jendso/bvac150.148.

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Abstract Introduction Immune check point inhibitors have become breakthrough therapy for many types of cancers. They inhibit one of two immune regulatory pathways, the cytotoxic T-lymphocyte antigen 4 (CTLA-4), and 'programmed death-1' (PD-1) and (PD-L1) pathways. Removing immune regulation allows for anti-cancer immune responses. They also cause immune related endocrine dysfunction such as hypophysitis, thyroiditis, diabetes mellitus (DM) and primary adrenal insufficiency (AI). We describe a patient on Pembrolizumab (PEM) (an anti-PD-1 inhibitor) who presented with new onset DM, euglycemic diabetic ketoacidosis (DKA) with simultaneous secondary AI. Case report 54-year-old woman with stage 4 non-small cell carcinoma of the lung (NSCLC) with known brain metastasis, was under therapy with carboplastin, paclitaxel and PEM, presented with headache, blurry vision and altered mental status. She had past history of Graves’ disease s/p radioactive iodine therapy, currently on levothyroxine. For two weeks, she had decreased oral intake, and generalized weakness. Upon presentation, she was cachectic, BP 152/65, pulse 117 and confabulating. Laboratory evaluation showed: serum glucose 72 mg/dL, Na 139 mmol/L, K 3.2 mmol/L, Cl 113 mmol/L, HCO3 11 mmol/L, anion gap 15 mmol/L, beta-hydroxybutyrate 4.8 mmol/L, lactic acid 0.7 mmol/L, venous pH 7.2 and base excess -16.6 mmol/L. The delta-delta gap was 10 mmol/L, compatible with a mixed anion-gap and hyperchloremic acidosis (HCA). Antibodies to GAD-65, and Zinc transporter-8 were negative. To evaluate euglycemia despite DKA, levels were obtained for serum cortisol 1 mcg/dL, and ACTH <1 pg/mL confirming secondary AI. MRI neuroimaging showed several metastatic brain lesions, a small pituitary gland without stalk enhancement or thickening. Management of euglycemic ketoacidosis required high dose glucose infusion (>10 g/hour), stress doses of hydrocortisone (HC), and infusion of low chloride solute for HCA. Conclusion Awareness of the potential for multi-endocrine dysfunction, directed us towards the urgent institution of therapy for DKA with supplementation of stress dose HC for presumed AI, the latter as a cause of relative "hypoglycemia". Central AI was confirmed with undetectable levels of cortisol and ACTH. Although less frequent than with CTLA-4 inhibitors, PD-1 inhibitors are associated with hypophysitis even without abnormalities on pituitary MRI. The DM (associated with PD-1 inhibitors) although autoimmune is nature, is "antibody" positive approximately 50% of the time. Further therapy for both euglycemic DKA and HCA required adjustment of the conventional management for DKA. To our knowledge this is the first reported case of Euglycemic DKA and secondary AI due to PD-1 inhibitors per literature review. Reference: Walters AGB, BraatvedtG G. Endocrine adverse effects of immune check point inhibitors . Intern Med J. 2021Jul;51(7): 1016-1020. doi: 10.111/imj . 14992. PMID: 34278695. Hattersley R, Nana M,Lansdown AJ. Endocrine complications of immunopathies: a review . ClinMed(Lond).2021 Mar;21(2): e212-e222. doi: 10.7861/clinmed.2020-0827. PMID: 33762389;PMCID: PMC8002767 Presentation: No date and time listed
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15

Kapoor, Vidit, und Olivier Rixe. „Toxicity of PD-1/CTLA-4 inhibitor immunotherapy among elderly patients.“ Journal of Clinical Oncology 37, Nr. 15_suppl (20.05.2019): e14139-e14139. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14139.

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e14139 Background: The use of Immune check point inhibitors in advanced metastatic melanoma is becoming increasingly common especially in the elderly population. With metastatic melanoma being mostly a disease of the elderly, the safety and toxicity profile of immune check point inhibitors in this population group continues to remain controversial. Prior studies have hypothesized that due to reduced immune responses in the elderly, toxicity to immune check point inhibitors is expected to be low. In this study we aim to analyze the association of check point inhibitor induced immuno-toxicity with age. Methods: We analyzed 108 patients with stage 4 metastatic melanoma who were treated with anti-PD1 and/or anti-CTLA-4 immunotherapy. Out of these patients, 58 (53.7%) were 65 or more years old and 50 (46.3%) were < 65 years old. Overall, 64 (59.3%) patients had autoimmune side effects; 35 (60.3%) were 65 years or older and 29 (48%) were < 65 years old. The most common side effects were dermatitis (n = 22, 20.4%) and colitis (n = 21, 19.4%). Incidences of various autoimmune side effects were calculated in both groups (65 years or older and < 65 years old). Fisher exact test was used to calculate p values Results: There was a significant difference between the incidence of dermatitis between the two groups. (51.4% in 65 years or older and 24.1% in < 65 years old group, p = 0.04). The incidence of colitis was more in the 65 years or older group (37.1%) as compared to < 65 years group (31.1%) however results were not statistically significant (p = 0.79). Similarly, there was no significant difference in other autoimmune side effects including hepatitis, arthritis, pneumonitis, thyroiditis, hypophysitis, adrenalitis, anemia and thrombocytopenia between the two groups. Also, there was no significant difference in the incidence of different grades of side effects (1 to 4) between the two groups. Conclusions: Patients who are 65 years or older can safely tolerate immunotherapy as compared to patients < 65 years old but with an increased risk of dermatitis. These data should be validated by a larger study population.
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Schmidinger, Manuela, Irene Resch, Harun Fajkovic, Mesut Remzi, Shahrokh F. Shariat und Jens Bedke. „Dual immune check point blockade or immune check point-tyrosine kinase inhibitor combination: as a first-line treatment in metastatic renal cell carcinoma?“ Current Opinion in Urology 31, Nr. 3 (11.03.2021): 270–75. http://dx.doi.org/10.1097/mou.0000000000000874.

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17

Thomas, Richard, Bibin Sebastian, Tom George, Noor Fatima Majeed, Temilola Akinola, Shawn L. Laferriere und Marta Braschi-Amirfarzan. „A review of the imaging manifestations of immune check point inhibitor toxicities“. Clinical Imaging 64 (August 2020): 70–79. http://dx.doi.org/10.1016/j.clinimag.2020.04.007.

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18

Mbaraonye, Uchenne, Lily Romero Karam, Cindy Nguyen, Deepa Gotur und Simon Yau. „IMMUNE CHECK POINT INHIBITOR-INDUCED ORGANIZING PNEUMONIA IN A LUNG TRANSPLANT PATIENT“. Chest 158, Nr. 4 (Oktober 2020): A1135—A1136. http://dx.doi.org/10.1016/j.chest.2020.08.1038.

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19

Arcari, Luca, Giacomo Tini, Giovanni Camastra, Federica Ciolina, Domenico De Santis, Domitilla Russo, Damiano Caruso, Massimiliano Danti und Luca Cacciotti. „Cardiac Magnetic Resonance Imaging in Immune Check-Point Inhibitor Myocarditis: A Systematic Review“. Journal of Imaging 8, Nr. 4 (05.04.2022): 99. http://dx.doi.org/10.3390/jimaging8040099.

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Immune checkpoint inhibitors (ICIs) are a family of anticancer drugs in which the immune response elicited against the tumor may involve other organs, including the heart. Cardiac magnetic resonance (CMR) imaging is increasingly used in the diagnostic work-up of myocardial inflammation; recently, several studies investigated the use of CMR in patients with ICI-myocarditis (ICI-M). The aim of the present systematic review is to summarize the available evidence on CMR findings in ICI-M. We searched electronic databases for relevant publications; after screening, six studies were selected, including 166 patients from five cohorts, and further 86 patients from a sub-analysis that were targeted for a tissue mapping assessment. CMR revealed mostly preserved left ventricular ejection fraction; edema prevalence ranged from 9% to 60%; late gadolinium enhancement (LGE) prevalence ranged from 23% to 83%. T1 and T2 mapping assessment were performed in 108 and 104 patients, respectively. When available, the comparison of CMR with endomyocardial biopsy revealed partial agreement between techniques and was higher for native T1 mapping amongst imaging biomarkers. The prognostic assessment was inconsistently assessed; CMR variables independently associated with the outcome included decreasing LVEF and increasing native T1. In conclusion, CMR findings in ICI-M include myocardial dysfunction, edema and fibrosis, though less evident than in more classic forms of myocarditis; native T1 mapping retained the higher concordance with EMB and significant prognostic value.
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Mathew Thomas, Vinay, Poorva Bindal, Swetha Ann Alexander und Kymberly McDonald. „Nivolumab-induced hepatitis: A rare side effect of an immune check point inhibitor“. Journal of Oncology Pharmacy Practice 26, Nr. 2 (25.03.2019): 459–61. http://dx.doi.org/10.1177/1078155219837342.

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Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3–6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.
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Das, Undurti N. „Bioactive lipids as modulators of immune check point inhibitors“. Medical Hypotheses 135 (Februar 2020): 109473. http://dx.doi.org/10.1016/j.mehy.2019.109473.

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22

Lleo, Ana, Lorenza Rimassa und Massimo Colombo. „Hepatotoxicity of immune check point inhibitors: Approach and management“. Digestive and Liver Disease 51, Nr. 8 (August 2019): 1074–78. http://dx.doi.org/10.1016/j.dld.2019.06.017.

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23

Kiyota, Naomi. „Immune check point inhibitors for head and neck cancer“. Toukeibu Gan 44, Nr. 4 (2018): 336–41. http://dx.doi.org/10.5981/jjhnc.44.336.

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24

Sørensen, A. S., M. Nørgaard Andersen, K. Juul-Madsen, C. Skejø, H. Schmidt, T. Vorup-Jensen und T. W. Kragstrup. „OP0130 IN VITRO CHARACTERIZATION OF INFLAMMATORY ARTHRITIS ASSOCIATED WITH IMMUNE CHECK POINT INHIBITION“. Annals of the Rheumatic Diseases 79, Suppl 1 (Juni 2020): 85.1–85. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1356.

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Background:During cancer treatment with immune checkpoint inhibitors (ICI) such as the anti-PD-1 antibody pembrolizumab, 2-4% of patients develop inflammatory arthritis as an immune related adverse event and half of patients with pre-existing inflammatory arthritis have disease flares. This type of adverse events shows striking similarities with traditional immune mediated inflammatory arthritis. However, the underlying immunological mechanisms of inflammatory arthritis associated with ICI are not fully understood.Objectives:We aimed to develop an in vitro model of inflammatory arthritis associated with ICI, and to use this model to investigate monocyte differentiation and activation following treatment with pembrolizumab.Methods:First, synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from patients with immune mediated inflammatory arthritis (rheumatoid arthritis and peripheral spondyloarthritis, n=22) and PBMCs from healthy controls were incubated with pembrolizumab and assessed for monocyte chemoattractant protein 1 (MCP-1) secretion by ELISA. Then, cytokine production in SFMCs was studied in more detail by the multiplex V-PLEX proinflammatory panel and by intracellular flow cytometry. Finally, pembrolizumab treated SFMCs were incubated with the different disease modifying anti-rheumatic drugs adalimumab, tocilizumab, tofacitinib, and baricitinib.Results:Pembrolizumab significantly increased MCP-1 production in the SFMCcultures (P=0.0031). In contrast, pembrolizumab did not change MCP-1 production by PBMCs from neither patients nor healthy controls (P=0.77 and P=0.43). Pembrolizumab also increased the production of TNFα (P=0.049), IFNγ (P=0.047), and IL-12p70 (P=0.031), but did not change the production of IL-6 (P=0.98). Among SFMCs treated with pembrolizumab there was an increased frequency of intermediate monocytes (P=0.044). Interestingly, pembrolizumab also increased the MCP-1 production within the intermediate monocytes only (P=0.028). In contrast, among SFMCs treated with LPS, only the classical monocyte subset was increased (P=0.0045) and MCP-1 production increased in both intermediate and classical monocyte subsets. Lastly, the TNFα inhibitor adalimumab and the Janus kinase inhibitors baricitinib and tofacitinib attenuated the pembrolizumab-induced MCP-1 production (P=0.0004, P=0.033, and P=0.025, respectively) while this was not seen with the IL-6 inhibitor tocilizumab (P=0.75).Conclusion:We have developed a very simple in vitro model of inflammatory arthritis associated with ICI. Using this model, we found that pembrolizumab specifically activated intermediate monocytes and induced TNFα, IFNγ, and IL-12p70 production, whereas IL-6 was unchanged. These findings were supported by effectful reduction of MCP-1 secretion with TNFα inhibition but not with IL-6 inhibition. This model could potentially be used to further study the effects of ICIs and the underlying immunological mechanisms of inflammatory arthritis associated with ICI.References:None.Disclosure of Interests:Anne Sofie Sørensen: None declared, Morten Nørgaard Andersen: None declared, Kristian Juul-Madsen: None declared, Cæcilie Skejø: None declared, Henrik Schmidt: None declared, Thomas Vorup-Jensen: None declared, Tue Wenzel Kragstrup Shareholder of: iBio Tech ApS, Consultant of: Bristol-Myers Squibb, Speakers bureau: TWK has engaged in educational activities talking about immunology in rheumatic diseases receiving speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, and UCB.
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Mudunov, A. M., A. V. Ignatova, A. S. Morozova, S. O. Podvyaznikov und Yu V. Alymov. „Combination of concurrent targeted and immune-therapy with nivolumab and cetuximab: new perspectives for squamous cell carcinoma treatment“. Head and Neck Tumors (HNT) 10, Nr. 3 (16.11.2020): 111–17. http://dx.doi.org/10.17650/2222-1468-2020-10-3-111-117.

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Head and neck squamous cell carcinoma (HNSCC) is the most common cancer among head and neck malignancies and causes of cancer death. More than 50 % of patiens have relapses within first 3 years after treatment, with median survival less than 6 months. Cetuximab is the first targeted agent for HNSCC, is considered as alternative regiment in case of intolerance to platinum-based chemotherapy, and also can activate an antigenspecific T-cell immunity in head and neck cancer patients. Nivolumab is a check-point inhibitor, that improves overall survival of patients with advanced recurrent/metastatic HNSCC, due to the CheckMate-141 study results. The results of phase II study сoncurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC showed a benefit for patients without prior check-point inhibitor exposure and overall well tolerated. Thus, we have 6 cases of HNSCC, treated with combination of nivolumab and cetuximab, resulted in durable (12 months) partial response or stabilization without severe adverse events. In our study, all 6 patients had prior check-point inhibitor exposure with nivolumab. Cetuximab was added to a treatment protocol after evidence-based progression during check-point inhibitor therapy. We demonstrate a case report of recurrent locally advanced HNSCC, treated with combination of nivolumab and cetuximab and resulted in stabilization. Only 1 patient had a progression after concurrent targeted and immune-therapy with nivolumab and cetuximab. New combination was well tolerated without severe adverse events. To our opinion, first results are challenging and we believe in great perspectives of comprehensive molecular profiling and combination of targeted and immune-therapy for better results.
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Elkayam, Natalie, und Shaurya Sharma. „Dual checkpoint inhibitor induced autoimmune encephalitis“. Archive of Oncology 25, Nr. 2 (2019): 22–24. http://dx.doi.org/10.2298/aoo181230003e.

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Immune checkpoint inhibitor therapy has become increasingly more used as a treatment modality for solid organ tumors. Nivolumab, anti-PD-1 and Ipilimumab, anti-CTLA-4 monoclonal antibodies are checkpoint inhibitors with well described immune related toxicities. Immune specific neurotoxicity is rare and not well elucidated in literature. We present a case of severe autoimmune encephalitis in a patient with metastatic renal cell carcinoma treated with both Nivolumab and Ipilimumab. A 53-year-old man with metastatic renal cell carcinoma presented due to visual and auditory hallucinations of sudden onset, confusion and weakness. Initial imaging and diagnostic workup did not demonstrate a clear source. However, a neurological etiology was suspected. It was concluded that the patient had autoimmune encephalitis induced by dual check point inhibitor therapy. This was further strengthened by his rapid response to systemic corticosteroid therapy. We present a summary of this case and its management and a review of literature on dual checkpoint inhibitor induced neurological adverse effects.
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Taylor, C., M. Reno und D. Sharma. „Secondary sclerosing cholangitis: a lesser known side effect of pembrolizumab therapy“. American Journal of Clinical Pathology 156, Supplement_1 (01.10.2021): S123—S124. http://dx.doi.org/10.1093/ajcp/aqab191.263.

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Abstract Introduction/Objective Immune check-point inhibitors have increasingly taken hold as mainstays of various cancer treatments, revolutionizing outcomes for individuals diagnosed with terminal malignancy. Hepatotoxicity is reported to occur in 2-10% patients, predominantly manifesting as a mixed cholestatic hepatitis pattern of injury. Cholangitis is a rare immune-mediated adverse event (irAE). We present a case of pembrolizumab-induced secondary sclerosing cholangitis presenting with multiple biliary strictures. Early recognition is crucial as these cases are resistant to treatment with steroids. Methods/Case Report 82-year-old woman with recurrent, metastatic, high grade urothelial carcinoma status post cystectomy and neoadjuvant chemotherapy, presented with new onset obstructive jaundice (alkaline phosphatase 958 U/L, aspartate aminotransferase of 331 U/L, alanine aminotransferase of 422 U/L, and total bilirubin of 19.8 mg/dL) following two weeks of pembrolizumab therapy. MRCP suggested intrahepatic biliary ductal dilation. ERCP showed multiple strictures involving hepatic bifurcation, left, right and intrahepatic ducts with beaded intrahepatic bile ducts. Liver biopsy showed expanded portal tracts with mixed inflammatory infiltrate, extensive bile duct injury, neutrophilic cholangitis, ductular proliferation, and perivenular cholestasis (10% dropout) concerning for mechanical obstruction. CK7 did not show ductopenia and immunostain IgG4 was negative. All autoimmune work-up was negative. Liver enzymes continued to rise despite multiple therapeutic stents, drains, high-dose corticosteroids, ursodiol and mycophenolate mofetil. The patient died five months later. Results (if a Case Study enter NA) NA Conclusion Pemrolizumab-induced secondary sclerosing cholangitis is a rare, hence under-recognized, adverse effect of check point inhibitor-mediated hepatotoxicity. It is important to recognize this association, as it has limited benefit from steroid therapy. Our finding of pembrolizumab-related SC adds to the growing body of literature of immune check-point inhibitor-related hepatobiliary injury and calls for further characterization of PD-1/PD-L1 inhibitor SC and its clinical implications.
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Ibraheim, Hajir, Esperanza Perucha und Nick Powell. „Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors“. Rheumatology 58, Supplement_7 (01.12.2019): vii17—vii28. http://dx.doi.org/10.1093/rheumatology/kez465.

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Abstract Immune check point inhibitor (CPI) therapy has revolutionized treatment paradigms for several cancers, but at the cost of triggering a diverse spectrum of immune-mediated injury to non-cancer tissues. The complex biology of these toxicities remains incompletely understood, partly because tissue acquisition from affected areas can be challenging to retrieve, thus hindering development of targeted therapy. Here, we review the literature describing pathology of immune-mediated tissue lesions including gastrointestinal, skin, rheumatic, pulmonary, cardiac, renal and hepatic lesions and highlight key immunological insights.
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Drommi, Fabiana, Alessia Calabrò, Grazia Vento, Gaetana Pezzino, Riccardo Cavaliere, Fausto Omero, Paola Muscolino et al. „Crosstalk between ILC3s and Microbiota: Implications for Colon Cancer Development and Treatment with Immune Check Point Inhibitors“. Cancers 15, Nr. 11 (24.05.2023): 2893. http://dx.doi.org/10.3390/cancers15112893.

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Type 3 innate lymphoid cells (ILC3s) are primarily tissue-resident cells strategically localized at the intestinal barrier that exhibit the fast-acting responsiveness of classic innate immune cells. Populations of these lymphocytes depend on the transcription factor RAR-related orphan receptor and play a key role in maintaining intestinal homeostasis, keeping host–microbial mutualism in check. Current evidence has indicated a bidirectional relationship between microbiota and ILC3s. While ILC3 function and maintenance in the gut are influenced by commensal microbiota, ILC3s themselves can control immune responses to intestinal microbiota by providing host defense against extracellular bacteria, helping to maintain a diverse microbiota and inducing immune tolerance for commensal bacteria. Thus, ILC3s have been linked to host–microbiota interactions and the loss of their normal activity promotes dysbiosis, chronic inflammation and colon cancer. Furthermore, recent evidence has suggested that a healthy dialog between ILC3s and gut microbes is necessary to support antitumor immunity and response to immune checkpoint inhibitor (ICI) therapy. In this review, we summarize the functional interactions occurring between microbiota and ILC3s in homeostasis, providing an overview of the molecular mechanisms orchestrating these interactions. We focus on how alterations in this interplay promote gut inflammation, colorectal cancer and resistance to therapies with immune check point inhibitors.
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Keyes, Erin, Muhammad B. Hammami und Kendall R. Beck. „2555 Immune Check Point Inhibitor Enteritis: A Case of Severe Duodenitis From Nivolumab Therapy“. American Journal of Gastroenterology 114, Nr. 1 (Oktober 2019): S1405. http://dx.doi.org/10.14309/01.ajg.0000599752.28233.77.

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31

Sanchez, Carlos A. Vergara, Rashid Alhusain, Jordan Christopher Ray und Julio Perez-Downes. „A CASE OF IMMUNE CHECK POINT INHIBITOR MEDIATED MYOPERICARDITIS: MANAGING A RARE ADVERSE REACTION“. Journal of the American College of Cardiology 83, Nr. 13 (April 2024): 3204. http://dx.doi.org/10.1016/s0735-1097(24)05194-5.

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Albarel, Frédérique, Frédéric Castinetti und Thierry Brue. „MANAGEMENT OF ENDOCRINE DISEASE: Immune check point inhibitors-induced hypophysitis“. European Journal of Endocrinology 181, Nr. 3 (September 2019): R107—R118. http://dx.doi.org/10.1530/eje-19-0169.

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In recent years, the development of immunotherapy has constituted a revolution in the therapy for many cancers, with a specific toxicity profile including endocrine immune-related adverse events. Immune check point inhibitors (ICI)-induced hypophysitis is a common endocrine side effect, particularly with CTLA-4 antibodies and combination therapy, with frequent hormonal deficiencies at diagnosis. It can be difficult to evoke such diagnosis as the initial clinical symptoms are not specific (headache, asthenia…); thus, patients receiving such immunomodulatory therapies should be closely monitored by systematic hormone measurements, especially in the first weeks of treatment. Usually, hormonal deficiencies improve, except for corticotroph function. Despite a lack of large prospective studies on ICI-induced hypophysitis, some detailed longitudinal cohort studies have focused on such cases of hypophysitis and allow for optimal monitoring, follow-up and management of patients with this immune-related adverse event. In the case of ICI-induced hypophysitis, patients need long-term multidisciplinary follow-up, with specific education for those patients with corticotropin deficiency to allow them to be autonomous with their treatment. In this review, based on a clinical case, we detail the most relevant and novel aspects related to the incidence, diagnosis, treatment, evolution and management of hypophysitis induced by immunotherapy, with a focus on possible mechanisms and current recommendations and guidelines. Lastly, we emphasize several key points, such as the absence of indication to systematically treat with high-dose glucocorticoid and the pursuit of immunotherapy in such hypophysitis. These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.
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Soares, Adriana, Rafael Carmo, Catarina Rodrigues, Inês Teles Grilo und Enrique Grande. „Chemotherapy Plus Immune Check-Point Inhibitors in Metastatic Bladder Cancer“. Bladder Cancer 6, Nr. 1 (28.03.2020): 1–8. http://dx.doi.org/10.3233/blc-190260.

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Orloff, Marlana, Ryan Weight, Matias E. Valsecchi und Takami Sato. „Immune Check Point Inhibitors Combination in Melanoma: Worth the Toxicity?“ Reviews on Recent Clinical Trials 11, Nr. 2 (01.05.2016): 81–86. http://dx.doi.org/10.2174/1574887111666160330120712.

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35

Kiyota, Naomi. „Current status of immune check point inhibitors for solid malignancy“. Annals of Oncology 27 (November 2016): vii5. http://dx.doi.org/10.1093/annonc/mdw453.

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36

Struble, Roger, Vikas Koppurapu, Derek Hupp, Yana Zemkova, Andrei Schwartz, Jeff Wilson und Charles Rappaport. „YIELD OF BAL IN PATIENTS RECEIVING IMMUNE CHECK POINT INHIBITORS“. Chest 158, Nr. 4 (Oktober 2020): A1935. http://dx.doi.org/10.1016/j.chest.2020.08.1675.

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37

Gupta, Tarana, und Nikhil Sai Jarpula. „Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status“. World Journal of Hepatology 16, Nr. 3 (27.03.2024): 353–65. http://dx.doi.org/10.4254/wjh.v16.i3.353.

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Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and has a high mortality rate. The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage. The recent description of the tumor microenvironment (TME) in HCC has provided a new concept of immunogenicity within the HCC. Virus-related HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells. This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors (ICIs). In addition, the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity. Therefore, data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.
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M. Guirgis, Helmy. „The Impact of The Immune Check Point Duration of use on Cost in Lung Cancer“. Pharmaceutics and Pharmacology Research 5, Nr. 6 (30.05.2022): 01–05. http://dx.doi.org/10.31579/2693-7247/086.

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Background: Monotherapy and combinations of Pembrolizumab (Pembro), Atezolizumab (Atezo) and Cemiplimab (Cemi), prolonged overall survival (OS) in advanced/metastatic non-small cell lung cancer (a/m NSCLC). Pembro demonstrated 5-year OS gain. The duration of therapy of the immune check point inhibitors (ICI) has not been defined. One-year adjuvant Durvalumab (Durv) and Atezo significantly prolonged OS. Neoadjuvant few cycles resulted in positive outcomes. Costs are relatively expensive, multiplying with prolonged use. The estimated 2019 CAR-T cost was $450,000. The Affordable Insulin bill 6833 capping insulin monthly cost at $35 was approved by the U.S. House of Representative. There are unmet needs for coherent drug cost policies and containment. We aimed 1- Explore the factors which impact ICI costs in lung cancer stages 2- Navigate cost-saving strategy based on generics, therapy duration and monotherapy utilization thresholds at $450,000 and $550,000 for combinations Methods: Clinical studies outcomes were quoted. Annual drug prices were calculated. Results: Estimated annual Pemetrexed (Peme) costs were $113,793, generic chemicals < $1,000 and Bevacizumab (Bev) $150,126 vs $148,000, mean 6 ICI. Pembro 2-year costs were $334,652. The 3- $501,978 and 5- $836,630 were above the $450,000. Atezo + Bev+ Peme combination had the highest 2-year $722,977 costs, above $550,000. Atezo + Peme costs were $422,725, Pembro + Peme $448,445 and Cemi + Peme $425,385, not significantly different. Costs decreased by 25% using generics. Extending ICI use by 6-12 months increased combination costs by 25-50%. Adjuvant 1-year Durv costs were $148,013 and Atezo $154,446, half the 2-year. Using response rates, cost of neoadjuvant Nivolumab (Nivo) 2-4 cycles were $25,000 - $50,000. Conclusion: Generics, short ICI duration use, neo-adjuvants, and utilization thresholds reduced costs.
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Chintalacheruvu, Lakshmi Manogna, Kushal Naha, Vamsi Krishna Chilluru und Donald C. Doll. „Review of neurological side effects associated with checkpoint inhibitor therapy in cancer patients.“ Journal of Clinical Oncology 38, Nr. 5_suppl (10.02.2020): 72. http://dx.doi.org/10.1200/jco.2020.38.5_suppl.72.

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72 Background: Checkpoint inhibitors have demonstrated efficacy in many cancer types. Neurological side effects are not well studied with check point inhibitors therapy. We conducted systematic review and meta analysis to evaluate the incidence of neurological side effects among various check point inhibitors. Methods: Eligible studies were searched for in PubMed and Google scholar. We searched for randomized controlled trials with cancer patients treated with check point inhibitors with neurological adverse effects. A total of 26 randomized controlled trials involving 6110 patients met eligibility criteria for the study. Results: Incidence rate of all grade neurological side effects include 5.6%(95% confidence interval [CI], 5.4-6.7%). Most common side effects include Headache (4.6%) (95% confidence interval [CI] 3.7-4.7%) followed by peripheral neuropathy (0.3%) (95% confidence interval [CI] 0.1-0.5%). Ipilimumab plus Nivolumab is associated with higher risk of headache and serious neurological side effects including myasthenia gravis, encephalitis, toxic encephalopathy and seizures. Conclusions: The incidence of neurological side effects associated with immune checkpoint inhibitors is low but not negligable. Patients on combination immunotherapy need more close monitoring for serious neurological side effects.
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kazuhiro, S., K. Sugiyama, K. Nozawa, Y. Funahashi, Y. Kogure, C. Kitagawa, S. Ichihara, R. Nishimura, T. Kubota und H. Saka. „Single-institute, retrospective study of metastatic uveal melanoma in the immune check point inhibitor era“. Annals of Oncology 29 (November 2018): ix106. http://dx.doi.org/10.1093/annonc/mdy439.005.

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41

Malkova, A. M., R. V. Orlova, N. V. Zhukova, A. R. Gubal und V. V. Sharoiko. „Analysis of possible markers of effective antitumor cellular immune response before starting therapy with immune check-point inhibitors“. Siberian journal of oncology 21, Nr. 2 (08.05.2022): 109–17. http://dx.doi.org/10.21294/1814-4861-2022-21-2-109-117.

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The aim of the study. to analyse possible markers of an effective antitumor cellular immune response.Material and methods. using the keywords «checkpoint inhibitors, immunotherapy, t-lymphocytes, exhausted t-lymphocytes, anti-tumor immune response», review and original articles (n=34) published from 2005 to 2020 in the Pubmed, Web Of Science, Elsevier databases were selected.Results. the study revealed possible markers reflecting a high activity of an adaptive immune response based on effective recognition of tumor antigens through MHC molecules, a sufficient number of T-lymphocytes and a predominance of T-cytotoxic cells, as well as a low level of expression of inhibitory receptors and small molecules. the presence of single nucleotide polymorphisms in the HLA-I and HLA-II genes encoding MHC-I and MHC-II proteins, respectively, a high level of lymphocytes, among which the most important is the predominance of CD8+ t cells and a low level of T-regulatory cells (T-reg), as well as the presence of single nucleotide polymorphisms in the genes encoding FcγR receptors of T-lymphocytes showed their predictive significance. the diagnostic significance of determining the expression of inhibitory receptors for T-lymphocytes (TIM3, LAG3, TIGIT), especially in combination with the determination of PD-1 expression, was also revealed.Conclusion. the results obtained may be relevant for applying new methods for the assessment of the functional activity of the T-cell immune response before starting therapy with checkpoint inhibitors, as well as for the development of new diagnostic panels, which may be of interest to employees of clinical diagnostic laboratories and research centers.
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Revathi, Duraisamy, Ganapathy Dhanraj und V. Ashok. „Immune check point inhibitors: A promising therapeutic approach in oral cancer“. Oral Oncology 132 (September 2022): 105977. http://dx.doi.org/10.1016/j.oraloncology.2022.105977.

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Khamnueva, L. Yu Khamnueva, K. A. Sergeeva Sergeeva, L. S. Andreeva Andreeva und A. V. Davydova Davydova. „Endocrinopathies induced by immune check point inhibitors. Optimal patient management tactics“. Pharmateca 12_2020 (23.11.2020): 8–13. http://dx.doi.org/10.18565/pharmateca.2020.12.8-13.

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44

Stringer, Bryan F., Nikhila Kethireddy, Alain Rizkallah und Konstadina Darsaklis. „MYOCARDITIS SECONDARY TO IMMUNE CHECK-POINT INHIBITORS: DIFFICULTIES IN ARRHYTHMIA MANAGEMENT“. Journal of the American College of Cardiology 75, Nr. 11 (März 2020): 2694. http://dx.doi.org/10.1016/s0735-1097(20)33321-0.

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Muhailan, Mohamad, und Ghassan Al-Shbool. „Pseudo-Wellens’ Syndrome Temporally Associated With Immune Check Point Inhibitors Use“. American Journal of the Medical Sciences 359, Nr. 1 (Januar 2020): e1-e2. http://dx.doi.org/10.1016/j.amjms.2019.07.006.

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Kim, Hyunseok, Soyeon Ahn, Hyungjin Kwon, Hsuan-Ju Chen, Inwon Park, Pilhan Kim und Akyildiz Kubra. „Abstract 2397: An advanced approach technique for tracking point between immune check point inhibitor and cancer cell mechanism in immune response motility by infiltration a breast cancer cell“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 2397. http://dx.doi.org/10.1158/1538-7445.am2023-2397.

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Abstract In Breast Cancer, Tumor-infiltrating lymphocyte (TIL) motility has been reported that it is reflecting tumor microenvironment response by adoptive cell therapy (ACT). ACT is well-known to be best applied for suppressing cancer cell growth with immune response and it also was well-known the immunotherapy. However, ACT response tracking by general analysis method included immunohistochemistry and flow cytometry was provided limited information for cancer therapy in recent years. Therefore, by assessing relationship immunotherapy marker, PD-L1, known as immune check point inhibitor and TIL using intravital microscopy in breast cancer model, we also imaged whether TIL response was related to immunotherapy following dependent on time point in a various breast cancer cell implanted mouse model such as 4T1 (mouse breast cancer cell), MDA-MB-231 (human triple negative breast cancer cell) and MCF7 (human breast cancer cell). These images result in PD-L1 expression was decreased in cancer cell implanted until 10days, whereas TIL expression increased in a various breast cancer cell when it is measuring displacement length, track mean velocity and confinement ratio called tumor microenvironment. These results indicated that we can imaged immune response related to TIL response in breast cancer cell line by intravital microscopy instead of general microscopy. It means that intravital microscope was an advanced approach technique to understand cancer mechanism accompanied by the immune response and established the method of high-resolution intravital cellular visualization compared to a general histopathological method for evaluating immune response in cancer tissue Citation Format: Hyunseok Kim, Soyeon Ahn, Hyungjin Kwon, Hsuan-Ju Chen, Inwon Park, Pilhan Kim, Akyildiz Kubra. An advanced approach technique for tracking point between immune check point inhibitor and cancer cell mechanism in immune response motility by infiltration a breast cancer cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2397.
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Roy, Arya Mariam, und Saby George. „Emerging resistance vs. losing response to immune check point inhibitors in renal cell carcinoma: two differing phenomena“. Cancer Drug Resistance 6, Nr. 3 (20.09.2023): 642–55. http://dx.doi.org/10.20517/cdr.2023.47.

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The introduction of immune checkpoint inhibitor (ICI) has revolutionized the treatment of metastatic renal cell carcinoma (mRCC) and has dramatically improved the outcomes of patients. The use of monotherapy or combinations of ICIs targeting PD-1/PD-L1 and CTLA-4, as well as the addition of ICIs with tyrosine kinase inhibitors, has significantly enhanced the overall survival of mRCC patients. Despite these promising results, there remains a subset of patients who either do not respond to treatment (primary resistance) or develop resistance to therapy over time (acquired resistance). Understanding the mechanisms underlying the development of resistance to ICI treatment is crucial in the management of mRCC, as they can be used to identify new targets for innovative therapeutic strategies. Currently, there is an unmet need to develop new predictive and prognostic biomarkers that can aid in the development of personalized treatment options for mRCC patients. In this review, we summarize several mechanisms of ICI resistance in RCC, including alterations in tumor microenvironment, upregulation of alternative immune checkpoint pathways, and genetic and epigenetic changes. Additionally, we highlight potential strategies that can be used to overcome resistance, such as combination therapy, targeted therapy, and immune modulation.
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Furnish, Robin, Heather Bear, Xin Wei und Timothy Phoenix. „MODL-29. EVALUATING TUMOR-IMMUNE INTERACTIONS IN MOUSE MODELS OF DIFFUSE INTRINSIC PONTINE GLIOMA“. Neuro-Oncology 22, Supplement_3 (01.12.2020): iii417. http://dx.doi.org/10.1093/neuonc/noaa222.602.

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Abstract BACKGROUND While adult gliomas show some level of immune cell infiltration, diffuse intrinsic pontine glioma (DIPG) is characterized as having an “immune cold” state. We have developed new immunocompetent mouse models of DIPG. These models faithfully recapitulate the pathological hallmarks of DIPG and provides a unique platform to investigate immune modulatory therapies and potential therapeutic benefits of check point inhibitor combination therapies. METHODS To evaluate the effects of CDK4/6 inhibition (CDK4/6i) on cell proliferation and immune interactions we performed a series of in vitro and in vivo studies using DIPG mouse models. In vitro assays included dose response curves, transcriptional profiling, and MHC1 expression. In vivo preclinical studies treated mouse models with CDK4/6i with or without immune check-point inhibitors (ICI). We also examined other candidate immune modulatory therapies in vitro. RESULTS CDK4/6i (Abemeciclib) reduced proliferation of DIPG cells derived from mouse models, and displayed a modest increase in immune activation by MHC1 expression and transcriptome. Pilot in vivo preclinical studies did not show any significant changes in DIPG proliferation or immune changes with CDK4/6i treatment, ICI treatment, or the combination of CDK4/6i + ICI. In vitro testing of other immune-modulatory drugs identified additional candidates that can be tested in vivo. CONCLUSION CDK4/6i displayed in vitro action, but lacked efficacy in DIPG mouse models in vivo. Further use of spontaneous DIPG mouse models will provide a rapid preclinical platform to evaluate in vivo tumor-immune interactions, drug efficacy, and mechanisms of resistance.
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De Felice, Francesca, Daniela Musio und Vincenzo Tombolini. „Immune Check-Point Inhibitors and Standard Chemoradiotherapy in Definitive Head and Neck Cancer Treatment“. Journal of Personalized Medicine 11, Nr. 5 (10.05.2021): 393. http://dx.doi.org/10.3390/jpm11050393.

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In head and neck cancer management, there is a need for tailored approaches to optimally implement clinical outcomes. Based on the assumption that efficacy and long-term toxicity are not satisfactory for standard concurrent platinum-based chemoradiotherapy, several trials have been designed to test whether induction immunotherapy and/or concomitant immunotherapy and radiotherapy result in improved survival and toxicity outcomes. Here, we present an overview of the most recent concomitant therapeutic strategies for head and neck cancer, focusing on the knowledge available regarding check-point inhibitors. The aim is to present the characteristics of the main check-point inhibitors and to summarize the clinical trials on the combination of immune check-point inhibitors and (chemo)radiotherapy in the definitive HNC setting, in order to provide a useful clinical tool for further research.
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Kikuchi, Yoshihiro, Hiroko Kouta, Takayoshi Asakawa, Miyuki Horikoshi, Tomoyuki Yoshikawa, Masashi Takano und Kenichi Furuya. „Roles of an immune-check point inhibitor (nivolumab) in heavily pretreated and platinum-resistant gynecologic cancers.“ Journal of Clinical Oncology 36, Nr. 15_suppl (20.05.2018): e17562-e17562. http://dx.doi.org/10.1200/jco.2018.36.15_suppl.e17562.

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