Sex Steroid Hormone Regulation of T-Cell Function and Antitumor Immunity

Cancer immunotherapy treatment has revolutionized cancer care. Of the many FDA-approved immunotherapies, immune checkpoint inhibitors are the most widely prescribed, given their utility in treating both solid and hematopoietic diseases and primary and metastatic malignancies. These therapies are dependent on co-opting the body's natural immunity, and thus conditions affecting the immune system can also determine therapeutic outcomes for patients with cancer. In this review, we examine one such naturally occurring immunomodulatory system: sex steroid hormones. Already thought to play a role in differing outcomes in infectious disease and transplant, sex steroid hormones may be contributing factors to differences in cancer occurrence and immunotherapy success between sexes. We will explore effects of steroid hormones on immune cells, specifically T cells, and the mechanisms through which they exert those effects as reported in the current literature. Androgens and progesterone are reported to exert largely immunosuppressive effects on T cells by promoting differentiation and expansion of immunosuppressive T-cell subpopulations. Interestingly, estrogen has been reported to have both immune-activating and immune-suppressing effects, both of which have the potential to affect the efficacy of immunotherapeutics. Therefore, patient hormonal status should be considered when prescribing immunotherapy for patients with cancer.