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Strength of immune selection in tumors varies with sex and age

Author

Listed:
  • Andrea Castro

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Rachel Marty Pyke

    (University of California San Diego
    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
    University of California San Diego
    University of California San Diego)

  • Maurizio Zanetti

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Hannah Carter

    (University of California San Diego
    University of California San Diego
    University of California San Diego
    University of California San Diego)

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.

Suggested Citation

  • Andrea Castro & Rachel Marty Pyke & Xinlian Zhang & Wesley Kurt Thompson & Chi-Ping Day & Ludmil B. Alexandrov & Maurizio Zanetti & Hannah Carter, 2020. "Strength of immune selection in tumors varies with sex and age," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17981-0
    DOI: 10.1038/s41467-020-17981-0
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    Cited by:

    1. Xinyu Bai & Grace H. Attrill & Tuba N. Gide & Peter M. Ferguson & Kazi J. Nahar & Ping Shang & Ismael A. Vergara & Umaimainthan Palendira & Ines Pires Silva & Matteo S. Carlino & Alexander M. Menzies , 2024. "Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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