Abstract 2116: Strength of immune selection in tumors varies with sex and age

Abstract

Abstract Individual MHC genotype constrains the mutational landscape during tumorigenesis. Immune checkpoint inhibition reactivates immunity against tumors that escaped immune surveillance in approximately 30% of cases. Recent studies demonstrated poorer response rates in female and younger melanoma patients. Although immune responses differ with sex and age, the role of MHC-based immune selection in this context is unknown. We found that tumors in younger and female individuals accumulated more poorly presented driver mutations than those in older and male patients, despite no differences in MHC genotype. Younger patients showed strongest effects of MHC-based driver mutation selection, with younger females showing compounded effects and nearly twice as much MHC-II based selection. This study presents the first evidence that strength of immune selection during tumor development varies with sex and age, and may influence the availability of mutant peptides capable of driving effective response to immune checkpoint inhibitor therapy. Citation Format: Andrea Castro, Rachel M. Pyke, Maurizio Zanetti, Hannah Carter. Strength of immune selection in tumors varies with sex and age [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2116.