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Updated: Sep 3, 2025

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Sex-biased adaptive immune regulation in cancer development and therapy
Johanna M Schafer1, Tong Xiao1, Hyunwoo Kwon1,2
1Pelotonia Institute for Immuno-Oncology, the Ohio State University Comprehensive Cancer Center - the James, Columbus, OH 43210, USA.
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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