Effect of the androgen receptor antagonist, enzalutamide, on human T cell expansion and function in vitro 3998

Abstract Description Sex differences in human immune responses are well-documented. In animal models, experimentally modulating sex hormones recapitulates many of these differences. Moreover, a recent study showed that testosterone treatment in female to male transgender individuals induced global changes towards a more “male” immune phenotype. Despite strong evidence that androgens modulate the immune system, the specific target cells and mechanisms by which this occurs in humans are largely unexplored. Here, we investigate whether the androgen receptor modulates human T cell responses in a T cell intrinsic manner. We stimulate purified human T cells in vitro in the presence or absence of enzalutamide, an FDA-approved androgen receptor antagonist used to treat prostate cancer. Enzalutamide at the time of TCR activation impairs T cell survival in short-term cultures. However, if provided after the first two days of TCR stimulation, enzalutamide increases T cell growth in long-term cultures. Moreover, preliminary data suggest enzalutamide may partially prevent loss of T cell function upon repeated TCR stimulation. Our data suggest that androgens can directly inhibit human T cell growth and function, a mechanism that might contribute to sex differences in immunity. This has ramifications for treatment of autoimmune disease and cancer immunotherapy, particularly for prostate cancer in which androgen deprivation and androgen receptor blockade are standards of care. Funding Sources Supported by NIH R15 CA267840-01A1 Topic Categories Immune Mechanisms of Human Disease (HUM)