Sex-biased Adaptive Immune Regulation in Cancer Development and Therapy

Overview

Journal iScience

Publisher Cell Press

Date 2022 Jul 26

PMID 35880048

Authors

Johanna M Schafer

Tong Xiao

Hyunwoo Kwon

Katharine Collier

Yuzhou Chang

Hany Abdel-Hafiz

Chelsea Bolyard

Dongjun Chung

Yuanquan Yang

Debasish Sundi

Qin Ma

Dan Theodorescu

Xue Li

Zihai Li

Affiliations

Soon will be listed here.

Abstract

The cancer research field is finally starting to unravel the mystery behind why males have a higher incidence and mortality rate than females for nearly all cancer types of the non-reproductive systems. Here, we explain how sex - specifically sex chromosomes and sex hormones - drives differential adaptive immunity across immune-related disease states including cancer, and why males are consequently more predisposed to tumor development. We highlight emerging data on the roles of cell-intrinsic androgen receptors in driving CD8 T cell dysfunction or exhaustion in the tumor microenvironment and summarize ongoing clinical efforts to determine the impact of androgen blockade on cancer immunotherapy. Finally, we outline a framework for future research in cancer biology and immuno-oncology, underscoring the importance of a holistic research approach to understanding the mechanisms of sex dimorphisms in cancer, so sex will be considered as an imperative factor for guiding treatment decisions in the future.

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