Significant association between tumor mutational burden and immune-related adverse events during immune checkpoint inhibition therapies.

Abstract

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.

• Authors: Csaba Kerepesi, Tibor Bakacs, Ralph W Moss, Shimon Slavin, Colin C Anderson
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 69 Issue 5 Pg. 683-687 (May 2020) ISSN: 1432-0851 [Electronic] Germany
• PMID: 32152702 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents, Immunological

Topics

• Adverse Drug Reaction Reporting Systems (statistics & numerical data)
• Antigens, Neoplasm (genetics, immunology)
• Antineoplastic Agents, Immunological (adverse effects)
• Drug-Related Side Effects and Adverse Reactions (genetics, immunology)
• Humans
• Mutation
• Neoplasms (drug therapy, genetics, immunology)
• Self Tolerance (drug effects, genetics)
• T-Lymphocytes (drug effects, immunology)