Our immune system can be likened to an army with patrolling soldiers—one of which is called T cells. Cancer is known to have the ability to evade the radar of our immune system's T cell soldiers, posing a unique threat for the body as it is unable to identify and destroy unwanted cancer cells. Males, in particular, seem to have weakened T cells due to the actions of androgens in the setting of bladder cancer.
Tumor-specific T cells are known to undergo dysfunction and exhaustion, resulting in a diminished ability to fight cancer cells (1). As recently featured, our study showed how androgen activity weakened the adaptive immune system in males (2). Specifically, the predominant male sex hormone androgen promoted CD8+ T cell exhaustion in the tumor microenvironment.
Androgens have also been shown to be immunosuppressive by inhibiting the function of macrophages, NK cells and T cells. These findings are therapeutically relevant due to the rise in immunotherapy. If the immune system is differentially affected by sex hormones, male and female response to immunotherapy is likely not uniform.
At the BCGSP, we are investing our efforts to better understand how sex hormones and immune cells interact in males and females. This will help future clinicians optimize the effect of androgen deprivation therapy and immunotherapy in both male and female BC patients.
1) McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. Annual Review of Immunology. 2019;37(1):457-95.
2) Kwon H, Schafer JM, Song NJ, Kaneko S, Li A, Xiao T, Ma A, Allen C, Das K, Zhou L, Riesenberg B, Chang Y, Weltge P, Velegraki M, Oh DY, Fong L, Ma Q, Sundi D, Chung D, Li X, Li Z. Androgen conspires with the CD8+ T cell exhaustion program and contributes to sex bias in cancer. Sci Immunol. 2022 Jul;7(73):eabq2630. doi: 10.1126/sciimmunol.abq2630. Epub 2022 Jul 1. PMID: 35420889.