Strength of immune selection in tumors varies with sex and age

Andrea Castro, Rachel Marty Pyke, Xinlian Zhang, Wesley Kurt Thompson, Chi-Ping Day, Ludmil B. Alexandrov, Maurizio Zanetti and Hannah Carter ()
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Andrea Castro: University of California San Diego
Rachel Marty Pyke: University of California San Diego
Xinlian Zhang: University of California San Diego
Wesley Kurt Thompson: University of California San Diego
Chi-Ping Day: National Institutes of Health
Ludmil B. Alexandrov: University of California San Diego
Maurizio Zanetti: University of California San Diego
Hannah Carter: University of California San Diego

Nature Communications, 2020, vol. 11, issue 1, 1-9

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 patients. Although immune responses differ with sex and age, the role of MHC-based immune selection in this context is unknown. We find that tumors in younger and female individuals accumulate more poorly presented driver mutations than those in older and male patients, despite no differences in MHC genotype. Younger patients show the 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 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.

Date: 2020
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DOI: 10.1038/s41467-020-17981-0

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