Significant association between tumor mutational burden and immune-related adverse events during immune checkpoint inhibition therapies.
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アブストラクト More than 2000 immuno-oncology agents are being tested or are in use as a result of the cancer immunotherapy revolution. Manipulation of co-inhibitory receptors has achieved tumor eradication in a minority of patients, but widespread immune-related adverse events (irAEs) compromised tolerance to healthy self-tissues in the majority. We have proposed that a major mechanism of irAEs is similar to a graft-versus-malignancy effect of graft-versus-host disease. To verify our hypothesis, we retrieved post-marketing data of adverse events from the U.S. Food and Drug Administration Adverse Event Reporting System. A significant positive correlation was revealed in 7677 patients between the reporting odds ratio of irAEs during immune checkpoint inhibitor therapy and the corresponding tumor mutational burden across 19 cancer types. These results can be interpreted to mean that the ICI drugs unleashed T cells against "altered-self," self, and tumors resulting in better overall survival. ジャーナル名 Cancer immunology, immunotherapy : CII 投稿日 2020/3/11 投稿者 Kerepesi, Csaba; Bakacs, Tibor; Moss, Ralph W; Slavin, Shimon; Anderson, Colin C 組織名 Institute for Computer Science and Control (SZTAKI), Kende u 13-17, Budapest,;1111, Hungary. kerepesi@sztaki.hu.;Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur,;Boston, MA, 02115, USA. kerepesi@sztaki.hu.;PRET Therapeutics Ltd., Budapest, 1124, Hungary.;Moss Reports, 104 Main Street Unit 1422, Blue Hill, ME, 04614-1422, USA.;Biotherapy International, The Center for Innovative Cancer Immunotherapy and;Cellular Medicine, Weizmann Center, 14 Weizmann Street Floor 15, Suite 1503,;64239, Tel Aviv, Israel.;Departments of Surgery and Medical Microbiology and Immunology, Alberta Diabetes;Institute, Alberta Transplant Institute, University of Alberta, Edmonton, AB, T6G;2E1, Canada. colinand@ualberta.ca. Pubmed リンク https://www.ncbi.nlm.nih.gov/pubmed/32152702/ -
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