Sex differences in innate immune cell responses: Impact on cancer immunity and response to therapy

Sex hormones regulate innate and adaptive immune responses to infection, autoimmunity, and carcinogenesis through genomic and non-genomic mechanisms. Estrogen, progesterone, and androgen receptors are widely expressed on immune cells and modulate their functional responses to pathological insults. While the impact of biological sex on infection, autoimmunity, and cancer risk has long been appreciated, their impact on response to cancer therapy is only beginning to be explored. Combinatorial strategies are being leveraged in the clinic to elicit antitumor immune responses, but the role of sex and hormones remains underexplored. Given that hormones impact both innate and adaptive immune responses, their interplay within the overall treatment regimen needs to be better understood, particularly for younger patients whose hormone levels remain relatively high, and for aging patients whose immune system divergence evolves despite reduced hormone levels. Herein, we review the interaction between hormones and the innate immune system and its implications for anti-cancer therapy.