{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:32:27Z","timestamp":1792801947084,"version":"4.5.0"},"reference-count":167,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Oradea, Oradea, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Immunotherapy, which stimulates the body\u2019s immune system, has received a considerable amount of press in recent years because of its powerful benefits. Cancer immunotherapy has shown long-term results in patients with advanced disease that are not seen with traditional chemotherapy. Immune checkpoint inhibitors, cytokines like interleukin 2 (IL-2) and interferon-alpha (IFN), and the cancer vaccine sipuleucel-T have all been licensed and approved by the FDA for the treatment of various cancers. These immunotherapy treatments boost anticancer responses by stimulating the immune system. As a result, they have the potential to cause serious, even fatal, inflammatory and immune-related side effects in one or more organs. Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell therapy are two immunotherapy treatments that are increasingly being used to treat cancer. Following their widespread usage in the clinic, a wave of immune-related adverse events (irAEs) impacting virtually every system has raised concerns about their unpredictability and randomness. Despite the fact that the majority of adverse effects are minimal and should be addressed with prudence, the risk of life-threatening complications exists. Although most adverse events are small and should be treated with caution, the risk of life-threatening toxicities should not be underestimated, especially given the subtle and unusual indications that make early detection even more difficult. Treatment for these issues is difficult and necessitates a multidisciplinary approach involving not only oncologists but also other internal medicine doctors to guarantee quick diagnosis and treatment. This study\u2019s purpose is to give a fundamental overview of immunotherapy and cancer-related side effect management strategies.<\/jats:p>","DOI":"10.3390\/molecules27123798","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"3798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Emerging Management Approach for the Adverse Events of Immunotherapy of Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-283X","authenticated-orcid":false,"given":"Md. Mominur","family":"Rahman","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapan","family":"Behl","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Rezaul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Noor","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Mohaimenul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Albarrati","sequence":"additional","affiliation":[{"name":"Rehabilitation Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Albratty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemsitry, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-7270","authenticated-orcid":false,"given":"Abdulkarim M.","family":"Meraya","sequence":"additional","affiliation":[{"name":"Practice Research Unit, Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45124, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-1292","authenticated-orcid":false,"given":"Simona Gabriela","family":"Bungau","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"},{"name":"Doctoral School of Biomedical Sciences, University of Oradea, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Whiteside, T.L. (2016). Tumor-derived exosomes and their role in tumor-induced immune suppression. Vaccines, 4.","DOI":"10.3390\/vaccines4040035"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3978","DOI":"10.1200\/JCO.21.01992","article-title":"Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline","volume":"39","author":"Santomasso","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1172\/JCI83871","article-title":"Cancer immunotherapy: Harnessing the immune system to battle cancer","volume":"125","author":"Yang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kumar, P., Saini, S., and Prabhakar, B.S. (2020). Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis. In , , 2020; pp 29\u201335. Seminars in Cancer Biology, Elsevier.","DOI":"10.1016\/j.semcancer.2019.01.006"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101370","DOI":"10.1016\/j.beem.2019.101370","article-title":"New insight in endocrine-related adverse events associated to immune checkpoint blockade","volume":"34","author":"Elia","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"vii59","DOI":"10.1093\/rheumatology\/kez308","article-title":"Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors","volume":"58","author":"Weinmann","year":"2019","journal-title":"Rheumatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1080\/21645515.2015.1129478","article-title":"Ipilimumab (Anti-Ctla-4 Mab) in the treatment of metastatic melanoma: Effectiveness and toxicity management","volume":"12","author":"Savoia","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rauf, A., Abu-Izneid, T., Khalil, A.A., Imran, M., Shah, Z.A., Emran, T.B., Mitra, S., Khan, Z., Alhumaydhi, F.A., Aljohani, A.S., and Khan, I. (2021). Berberine as a potential anticancer agent: A comprehensive review. Molecules, 26.","DOI":"10.3390\/molecules26237368"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.lungcan.2018.07.044","article-title":"Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi)","volume":"124","author":"Dudnik","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113041","DOI":"10.1016\/j.biopha.2022.113041","article-title":"Pharmacotherapy, Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology","volume":"150","author":"Rahman","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1002\/hep.30337","article-title":"Challenges and opportunities in the clinical development of immune checkpoint inhibitors for hepatocellular carcinoma","volume":"69","author":"Flynn","year":"2019","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1177\/1060028018809522","article-title":"Tildrakizumab: A Review of Phase II and III Clinical Trials","volume":"53","author":"Kolli","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1080\/14712598.2018.1533951","article-title":"Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia","volume":"18","author":"Thomas","year":"2018","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.2217\/imt-2017-0072","article-title":"CAR-T cells and allogeneic hematopoietic stem cell transplantation for relapsed\/refractory B-cell acute lymphoblastic leukemia","volume":"9","author":"Liu","year":"2017","journal-title":"Immunotherapy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1093\/annonc\/mdv182","article-title":"A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors","volume":"26","author":"Chen","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s40263-018-0582-9","article-title":"Neurotoxicity associated with CD19-targeted CAR-T cell therapies","volume":"32","author":"Gust","year":"2018","journal-title":"CNS Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2217\/fon.15.222","article-title":"Risk of endocrine complications in cancer patients treated with immune check point inhibitors: A meta-analysis","volume":"12","author":"ElHalawani","year":"2016","journal-title":"Future Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_20","first-page":"1103","article-title":"Monitoring the effects of treatment in colon cancer cells using immunohistochemical and histoenzymatic techniques","volume":"56","author":"Pallag","year":"2015","journal-title":"Rom. J. Morphol. Embriol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1634\/theoncologist.2019-0637","article-title":"Immune-Related Adverse Events and Immune Checkpoint Inhibitor Efficacy in Patients with Gastrointestinal Cancer with Food and Drug Administration-Approved Indications for Immunotherapy","volume":"25","author":"Das","year":"2020","journal-title":"Oncologist"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102310","DOI":"10.1016\/j.jaut.2019.102310","article-title":"Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells","volume":"104","author":"Alissafi","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1016\/S1470-2045(17)30074-8","article-title":"iRECIST: Guidelines for response criteria for use in trials testing immunotherapeutics","volume":"18","author":"Seymour","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/S0140-6736(18)30789-X","article-title":"International validation of the consensus Immunoscore for the classification of colon cancer: A prognostic and accuracy study","volume":"391","author":"Mlecnik","year":"2018","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1016\/S1470-2045(19)30413-9","article-title":"Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: Extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial","volume":"20","author":"Motzer","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1200\/JCO.2007.12.3604","article-title":"Survival for patients with invasive cutaneous melanoma among ethnic groups: The effects of socioeconomic status and treatment","volume":"26","author":"Zell","year":"2008","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91795","DOI":"10.18632\/oncotarget.20030","article-title":"Excellent response to chemotherapy post immunotherapy","volume":"8","author":"Dwary","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/CMR.0000000000000669","article-title":"Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients","volume":"30","author":"Aguilera","year":"2020","journal-title":"Melanoma Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9532","DOI":"10.1200\/JCO.2018.36.15_suppl.9532","article-title":"Activity of targeted therapy after failure of first-line immunotherapy in BRAF-mutant metastatic melanoma","volume":"36","author":"Xia","year":"2018","journal-title":"Am. Soc. Clin.Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3747\/co.27.5223","article-title":"A review of cancer immunotherapy: From the past, to the present, to the future","volume":"27","author":"Esfahani","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature10673","article-title":"Cancer immunotherapy comes of age","volume":"480","author":"Mellman","year":"2011","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/ni1102-991","article-title":"Cancer immunoediting: From immunosurveillance to tumor escape","volume":"3","author":"Dunn","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1470-2045(13)70510-2","article-title":"Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): A randomised, double-blind, phase 3 trial","volume":"15","author":"Butts","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41584-018-0074-9","article-title":"Rheumatic immune-related adverse events from cancer immunotherapy","volume":"14","author":"Calabrese","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1200\/JCO.2016.66.4581","article-title":"Surrogate End Points and Their Validation in Oncology Clinical Trials","volume":"34","author":"Zhao","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fonc.2018.00086","article-title":"Anti-PD-1 and anti-CTLA-4 therapies in cancer: Mechanisms of action, efficacy, and limitations","volume":"8","author":"Seidel","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cll.2017.06.001","article-title":"The immunology of melanoma","volume":"37","author":"Ko","year":"2017","journal-title":"Clin. Lab. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1097\/01.sla.0000247058.43243.7b","article-title":"Tumor infiltrating T lymphocytes in colorectal cancer: Tumor-selective activation and cytotoxic activity in situ","volume":"244","author":"Koch","year":"2006","journal-title":"Ann. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/path.2774","article-title":"Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: Cohort study and literature review","volume":"222","author":"Nosho","year":"2010","journal-title":"J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9037217","DOI":"10.1155\/2020\/9037217","article-title":"Expanding the scope of immunotherapy in colorectal cancer: Current clinical approaches and future directions","volume":"2020","author":"Kreidieh","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"173819","DOI":"10.1016\/j.ejphar.2020.173819","article-title":"Current advancements and future perspectives of immunotherapy in colorectal cancer research","volume":"893","author":"Kishore","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/jebm.12322","article-title":"Advances in evidence-based medicine for immunotherapy of non-small cell lung cancer","volume":"11","author":"Dong","year":"2018","journal-title":"J. Evid.-Based Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7412","DOI":"10.1158\/1078-0432.CCR-09-1624","article-title":"Guidelines for the evaluation of immune therapy activity in solid tumors: Immune-related response criteria","volume":"15","author":"Wolchok","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1056\/NEJMoa1613493","article-title":"First-line nivolumab in stage IV or recurrent non\u2013small-cell lung cancer","volume":"376","author":"Carbone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1158\/1078-0432.CCR-17-1341","article-title":"Early assessment of lung cancer immunotherapy response via circulating tumor DNA","volume":"24","author":"Goldberg","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1200\/JCO.2015.64.0391","article-title":"Evaluation of immune-related response criteria and RECIST v1. 1 in patients with advanced melanoma treated with pembrolizumab","volume":"34","author":"Hodi","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40644-019-0281-x","article-title":"iRECIST: How to do it","volume":"20","author":"Persigehl","year":"2020","journal-title":"Cancer Imaging."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/phar.1643","article-title":"Immune checkpoint inhibitors: New insights and current place in cancer therapy","volume":"35","author":"Jean","year":"2015","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"255","DOI":"10.6004\/jnccn.2019.0013","article-title":"Management of immunotherapy-related toxicities, version 1.2019, NCCN clinical practice guidelines in oncology","volume":"17","author":"Thompson","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1146\/annurev.immunol.19.1.565","article-title":"CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy","volume":"19","author":"Chambers","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nm.4321","article-title":"Is autoimmunity the Achilles\u2019 heel of cancer immunotherapy?","volume":"23","author":"June","year":"2017","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1056\/NEJMp1510079","article-title":"Releasing the brakes on cancer immunotherapy","volume":"373","author":"Ribas","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000437178","article-title":"Immune checkpoint inhibitors","volume":"42","author":"Haanen","year":"2015","journal-title":"Immuno-Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1056\/NEJMra1514296","article-title":"Molecular and biochemical aspects of the PD-1 checkpoint pathway","volume":"375","author":"Boussiotis","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/S1470-2045(18)30700-9","article-title":"Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial","volume":"19","author":"Hodi","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","article-title":"Fortgeschrittenes Nieren-zellkarzinom: Nivolumab plus Ipilimumab versus Sunitinib","volume":"378","author":"Motzer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck","volume":"375","author":"George","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1200\/JCO.2015.62.3397","article-title":"Safety and antitumor activity of anti\u2013PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer","volume":"33","author":"Hamanishi","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1470-2045(15)00094-7","article-title":"The place of PD-1 inhibitors in melanoma management","volume":"16","author":"Bowyer","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa1603702","article-title":"PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma","volume":"374","author":"Nghiem","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1056\/NEJMc1510353","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"373","author":"Diaz","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1200\/JCO.2012.48.3685","article-title":"Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: Results of an international phase II trial","volume":"31","author":"Armand","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S1470-2045(13)70551-5","article-title":"Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: A single group, open-label, phase 2 trial","volume":"15","author":"Westin","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1056\/NEJMoa1104621","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"364","author":"Robert","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e300-3","DOI":"10.1200\/JCO.2012.45.9495","article-title":"Continued response off treatment after BRAF inhibition in refractory hairy cell leukemia","volume":"31","author":"Dietrich","year":"2013","journal-title":"J. Clin.Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Tiako Meyo, M., Jouinot, A., Giroux-Leprieur, E., Fabre, E., Wislez, M., Alifano, M., Leroy, K., Boudou-Rouquette, P., Tlemsani, C., and Khoudour, N. (2020). Predictive value of soluble PD-1, PD-L1, VEGFA, CD40 ligand and CD44 for nivolumab therapy in advanced non-small cell lung cancer: A case-control study. Cancers, 12.","DOI":"10.3390\/cancers12020473"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e11936","DOI":"10.1097\/MD.0000000000011936","article-title":"Comparative analysis of immune checkpoint inhibitors and chemotherapy in the treatment of advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials","volume":"97","author":"Khan","year":"2018","journal-title":"Medicine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41467-022-27960-2","article-title":"Immune-related adverse events and the balancing act of immunotherapy","volume":"13","author":"Conroy","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Olsen, T.A., Zhuang, T.Z., Caulfield, S., Martini, D.J., Brown, J.T., Carthon, B.C., Kucuk, O., Harris, W., Bilen, M.A., and Nazha, B. (2022). Advances in Knowledge and Management of Immune-Related Adverse Events in Cancer Immunotherapy. Front. Endocrinol., 354.","DOI":"10.3389\/fendo.2022.779915"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"k793","DOI":"10.1136\/bmj.k793","article-title":"Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: Systematic review and meta-analysis","volume":"360","author":"Baxi","year":"2018","journal-title":"BMJ"},{"key":"ref_78","first-page":"5671","article-title":"Immune-related adverse events during anticancer immunotherapy: Pathogenesis and management","volume":"14","author":"Stucci","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_79","unstructured":"Ban, B., Crowe, J., and Graham, R. (2017). Rheumatology case report immune-related aortitis associated with ipilimumab. Rheumatologist, 11."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Park, H., Cho, M., Do, Y., Park, J.-K., Bae, S.-J., Joo, J., and Ha, K.-T. (2022). Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation. Pharmaceuticals, 15.","DOI":"10.3390\/ph15010053"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Corb Aron, R.A., Abid, A., Vesa, C.M., Nechifor, A.C., Behl, T., Ghitea, T.C., Munteanu, M.A., Fratila, O., Andronie-Cioara, F.L., Toma, M.M., and Bungau, S. (2021). Recognizing the Benefits of Pre-\/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030618"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1530\/EJE-17-0810","article-title":"The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma","volume":"178","author":"Scott","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1158\/2326-6066.CIR-16-0237","article-title":"Comprehensive meta-analysis of key immune-related adverse events from CTLA-4 and PD-1\/PD-L1 inhibitors in cancer patients","volume":"5","author":"Je","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1200\/JCO.2015.66.1389","article-title":"Safety profile of nivolumab monotherapy: A pooled analysis of patients with advanced melanoma","volume":"35","author":"Weber","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fphar.2017.00049","article-title":"Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy","volume":"8","author":"Kumar","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Behl, T., Sharma, A., Sharma, L., Sehgal, A., Singh, S., Sharma, N., Zengin, G., Bungau, S., Toma, M.M., Gitea, D., Babes, E.E., Judea Pusta, C.T., and Bumbu, A.G. (2021). Current Perspective on the Natural Compounds and Drug Delivery Techniques in Glioblastoma Multiforme. Cancers, 13.","DOI":"10.3390\/cancers13112765"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Rahman, M.M., Islam, M.R., Islam, M.T., Harun-Or-Rashid, M., Islam, M., Abdullah, S., Uddin, M.B., Das, S., Rahaman, M.S., and Ahmed, M. (2022). Stem Cell Transplantation Therapy and Neurological Disorders: Current Status and Future Perspectives. Biology, 11.","DOI":"10.3390\/biology11010147"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1136\/jclinpath-2018-205143","article-title":"Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: Pathologists\u2019 perspective","volume":"71","author":"Karamchandani","year":"2018","journal-title":"J. Clin. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.jhep.2018.01.033","article-title":"Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors","volume":"68","author":"Michot","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ctrv.2016.02.001","article-title":"Management of toxicities of immune checkpoint inhibitors","volume":"44","author":"Spain","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1479-5876-11-75","article-title":"Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events","volume":"11","author":"Shahabi","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1634\/theoncologist.2018-0434","article-title":"Cases from the irAE Tumor Board: A multidisciplinary approach to a patient treated with immune checkpoint blockade who presented with a new rash","volume":"24","author":"Patil","year":"2019","journal-title":"Oncologist"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1634\/theoncologist.2018-0128","article-title":"A case of nivolumab-induced bullous pemphigoid: Review of dermatologic toxicity associated with programmed cell death protein-1\/programmed death ligand-1 inhibitors and recommendations for diagnosis and management","volume":"23","author":"Lopez","year":"2018","journal-title":"Oncologist"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/cup.13273","article-title":"Scleroderma-like skin changes induced by checkpoint inhibitor therapy","volume":"45","author":"Tjarks","year":"2018","journal-title":"J. Cutan. Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/annonc\/mdw640","article-title":"Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer","volume":"28","author":"Osorio","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1001\/jamaoncol.2016.1051","article-title":"Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review","volume":"2","author":"Friedman","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/ecco-jcc\/jjv227","article-title":"Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease","volume":"10","author":"Marthey","year":"2016","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"405","DOI":"10.12998\/wjcc.v7.i4.405","article-title":"Immune checkpoint inhibitor-induced colitis: A comprehensive review","volume":"7","author":"Som","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_100","first-page":"e1444","article-title":"Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma","volume":"13","author":"Moein","year":"2021","journal-title":"Cureus"},{"key":"ref_101","first-page":"bcr-2018-224913","article-title":"Severe inflammatory ileitis resulting in ileal perforation in association with combination immune checkpoint blockade for metastatic malignant melanoma","volume":"2018","author":"Mohamed","year":"2018","journal-title":"Case Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41424-018-0049-9","article-title":"Immune checkpoint inhibitor-associated colitis and hepatitis","volume":"9","author":"Reddy","year":"2018","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s40425-018-0408-9","article-title":"A whole-blood RNA transcript-based gene signature is associated with the development of CTLA-4 blockade-related diarrhea in patients with advanced melanoma treated with the checkpoint inhibitor tremelimumab","volume":"6","author":"Friedlander","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ctrv.2016.02.003","article-title":"Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy","volume":"45","author":"Eigentler","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1158\/1078-0432.CCR-15-2471","article-title":"Infliximab for IPILIMUMAB-related colitis","volume":"21","author":"Arriola","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.canlet.2019.04.018","article-title":"Management of immune related adverse events induced by immune checkpoint inhibition","volume":"456","author":"Teufel","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1097\/PAS.0000000000000453","article-title":"Ipilimumab-associated Hepatitis","volume":"39","author":"Johncilla","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.jfma.2020.08.019","article-title":"The non-invasive assessment of hepatic fibrosis","volume":"120","author":"Gheorghe","year":"2021","journal-title":"J. Formosan Medical Assoc."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4217529","DOI":"10.1155\/2022\/4217529","article-title":"Multifunctional therapeutic approach of nanomedicines against inflammation in cancer and aging","volume":"2022","author":"Rahman","year":"2022","journal-title":"J. Nanomater."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1530\/ERC-13-0499","article-title":"Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: A comprehensive retrospective review from a single institution","volume":"21","author":"Ryder","year":"2014","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11102-009-0193-z","article-title":"Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: Serious immune related adverse events across a spectrum of cancer subtypes","volume":"13","author":"Dillard","year":"2010","journal-title":"Pituitary"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"R153","DOI":"10.1530\/EJE-13-0434","article-title":"Endocrine side-effects of anti-cancer drugs: mAbs and pituitary dysfunction: Clinical evidence and pathogenic hypotheses","volume":"169","author":"Torino","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1210\/jc.2012-4075","article-title":"Endocrine side effects induced by immune checkpoint inhibitors","volume":"98","author":"Corsello","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1634\/theoncologist.2015-0509","article-title":"Immune checkpoint inhibitors: Review and management of endocrine adverse events","volume":"21","year":"2016","journal-title":"Oncologist"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non\u2013small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/CCO.0000000000000291","article-title":"Immune-mediated respiratory adverse events of checkpoint inhibitors","volume":"28","author":"Tabchi","year":"2016","journal-title":"Curr. Opin. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.aan4236","article-title":"Gut microbiome modulates response to anti\u2013PD-1 immunotherapy in melanoma patients","volume":"359","author":"Gopalakrishnan","year":"2018","journal-title":"Science"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1158\/2326-6066.CIR-15-0102","article-title":"Radiographic profiling of immune-related adverse events in advanced melanoma patients treated with ipilimumab","volume":"3","author":"Tirumani","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"109437","DOI":"10.1016\/j.biopha.2019.109437","article-title":"Diagnosis and management of immune related adverse events (irAEs) in cancer immunotherapy","volume":"120","author":"Liu","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1158\/1535-7163.MCT-17-0155","article-title":"Risk of pneumonitis associated with programmed cell death 1 inhibitors in cancer patients: A meta-analysis","volume":"16","author":"Zhang","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1089\/hum.2018.119","article-title":"Induced CD20 expression on B-cell malignant cells heightened the cytotoxic activity of chimeric antigen receptor engineered T cells","volume":"30","author":"Xu","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1172\/JCI85309","article-title":"CD19 CAR\u2013T cells of defined CD4+: CD8+ composition in adult B cell ALL patients","volume":"126","author":"Turtle","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_123","first-page":"188","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11926-018-0770-0","article-title":"Immune-related adverse events in cancer patients treated with immune checkpoint inhibitors","volume":"20","author":"Sandigursky","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_125","first-page":"125","article-title":"Advances in cancer immunology and cancer immunotherapy","volume":"21","author":"Voena","year":"2016","journal-title":"Discov. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Fridman, W.H., Meylan, M., Petitprez, F., Sun, C.-M., Italiano, A., and Saut\u00e8s-Fridman, C. (2022). B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome. Nat. Rev. Clin. Oncol., 1\u201317.","DOI":"10.1038\/s41571-022-00619-z"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Cassim, S., Vu\u010deti\u0107, M., \u017ddralevi\u0107, M., and Pouyssegur, J. (2021). Warburg and beyond: The power of mitochondrial metabolism to collaborate or replace fermentative glycolysis in cancer. Cancers, 12.","DOI":"10.3390\/cancers12051119"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-immunol-031210-101324","article-title":"Natural innate and adaptive immunity to cancer","volume":"29","author":"Vesely","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: The cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev.iy.12.040194.002005","article-title":"Tumor antigens recognized by T lymphocytes","volume":"12","author":"Boon","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti\u2013PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/infdis\/jix191","article-title":"Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy","volume":"215","author":"Gay","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1001294","article-title":"Sipuleucel-T immunotherapy for castration-resistant prostate cancer","volume":"363","author":"Kantoff","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1158\/1078-0432.CCR-11-0116","article-title":"Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy","volume":"17","author":"Rosenberg","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/s43018-021-00232-6","article-title":"Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression","volume":"2","author":"Vanhersecke","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000449342","article-title":"Immune checkpoint blockade in hepatocellular carcinoma: 2017 update","volume":"6","author":"Kudo","year":"2017","journal-title":"Liver Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Cassim, S., and Pouyssegur, J. (2019). Tumor microenvironment: A metabolic player that shapes the immune response. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010157"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.2217\/fon-2021-0688","article-title":"Precision oncology: A clinical and patient perspective","volume":"17","author":"Lassen","year":"2021","journal-title":"Futur. Oncol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Haanen, J., and Robert, C. (2015). Immune checkpoint inhibitors. Immuno-Oncology, Karger Publishers.","DOI":"10.1159\/000437178"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"CNS28","DOI":"10.2217\/cns-2018-0007","article-title":"Use of the Response Assessment in Neuro-Oncology (RANO) criteria in clinical trials and clinical practice","volume":"8","author":"Chukwueke","year":"2019","journal-title":"CNS Oncol."},{"key":"ref_142","first-page":"400","article-title":"Management of adverse events associated with cancer immunotherapy","volume":"71","author":"Laparra","year":"2021","journal-title":"Rev. Prat."},{"key":"ref_143","first-page":"e001754","article-title":"Strategies for improving the management of immune-related adverse events","volume":"8","author":"Naing","year":"2020","journal-title":"Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.bulcan.2020.04.018","article-title":"Immunoth\u00e9rapie des cancers bronchiques non \u00e0 petites cellules m\u00e9tastatiques, de la premi\u00e8re ligne \u00e0 la r\u00e9sistance et sa prise en charge","volume":"107","author":"Basse","year":"2020","journal-title":"Bull. Cancer"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.3389\/fonc.2020.585311","article-title":"Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events\u2014A Comprehensive Review","volume":"10","author":"Hommes","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrendo.2016.205","article-title":"Cancer immunotherapy\u2014Immune checkpoint blockade and associated endocrinopathies","volume":"13","author":"Byun","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2147\/ITT.S126227","article-title":"Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: A short review","volume":"6","author":"Yoest","year":"2017","journal-title":"ImmunoTargets Ther."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/js.2017-00432","article-title":"Patients with antithyroid antibodies are prone to develop destructive thyroiditis by nivolumab: A prospective study","volume":"2","author":"Kobayashi","year":"2018","journal-title":"J. Endocr. Soc."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1136\/annrheumdis-2018-213777","article-title":"Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1","volume":"78","author":"Mammen","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.jaad.2019.08.045","article-title":"BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors","volume":"82","author":"Ali","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.jtho.2021.06.024","article-title":"Beyond Steroids: Immunosuppressants in Steroid-Refractory or Resistant Immune-Related Adverse Events","volume":"16","author":"Luo","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41572-020-0160-6","article-title":"Immune-related adverse events of checkpoint inhibitors","volume":"6","author":"Brahmer","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3747\/co.25.4235","article-title":"Immune-related adverse events of immune checkpoint inhibitors: A brief review","volume":"25","author":"Myers","year":"2018","journal-title":"Curr. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e1248327","DOI":"10.1080\/2162402X.2016.1248327","article-title":"Peripheral blood Th9 cells are a possible pharmacodynamic biomarker of nivolumab treatment efficacy in metastatic melanoma patients","volume":"5","author":"Nonomura","year":"2016","journal-title":"OncoImmunology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1158\/1078-0432.CCR-09-1024","article-title":"A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma","volume":"15","author":"Weber","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1016\/S1470-2045(18)30828-3","article-title":"New therapeutic perspectives to manage refractory immune checkpoint-related toxicities","volume":"20","author":"Martins","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40425-017-0300-z","article-title":"Managing toxicities associated with immune checkpoint inhibitors: Consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group","volume":"5","author":"Puzanov","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1200\/JCO.2014.57.4756","article-title":"Vitiligo-like depigmentation in patients with stage III\u2013IV melanoma receiving immunotherapy and its association with survival: A systematic review and meta-analysis","volume":"33","author":"Teulings","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s40425-019-0805-8","article-title":"Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors","volume":"7","author":"Das","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e1742","DOI":"10.1002\/onco.13868","article-title":"Immune-related adverse events as clinical biomarkers in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors","volume":"26","author":"Martini","year":"2021","journal-title":"Oncologist"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1007\/s10637-017-0534-0","article-title":"Incidence of immune-related adverse events and its association with treatment outcomes: The MD Anderson Cancer Center experience","volume":"36","author":"Fujii","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s12020-019-02088-4","article-title":"Thyroid profile during the alternative Sunitinib dosing 2\/1 schedule in metastatic renal cell carcinoma","volume":"67","author":"Rizza","year":"2020","journal-title":"Endocrine"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Giannetta, E., La Salvia, A., Rizza, L., Muscogiuri, G., Campione, S., Pozza, C., Colao, A.A.L., and Faggiano, A. (2021). Are Markers of Systemic Inflammatory Response Useful in the Management of Patients With Neuroendocrine Neoplasms?. Front. Endocrinol., 565.","DOI":"10.3389\/fendo.2021.672499"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00432-019-02839-w","article-title":"Immune checkpoint blockade for Merkel cell carcinoma: Actual findings and unanswered questions","volume":"145","author":"Gallo","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e1911519","DOI":"10.1001\/jamanetworkopen.2019.11519","article-title":"Variation in the assessment of immune-related adverse event occurrence, grade, and timing in patients receiving immune checkpoint inhibitors","volume":"2","author":"Hsiehchen","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Al-Sadi, A.M., Al-Oweisi, F.A., Edwards, S.G., Al-Nadabi, H., and Al-Fahdi, A.M. (2015). Genetic analysis reveals diversity and genetic relationship among Trichoderma isolates from potting media, cultivated soil and uncultivated soil. BMC Microbiol., 15.","DOI":"10.1186\/s12866-015-0483-8"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3798\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:28:46Z","timestamp":1760138926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":167,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["molecules27123798"],"URL":"https:\/\/doi.org\/10.3390\/molecules27123798","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,13]]}}}