Sex differences in tissue-specific immunity and immunology

Biological sex exerts a substantial influence on the immune system and immune-related diseases. Males are more susceptible to the acute effects of viral disease and certain cancers, whereas females exhibit a more robust immune response that can make them prone to developing autoimmune complications. We reflect on the emerging appreciation of sex differences—governed by genetics, sex hormones, and environmental factors—in tissue immunity and immunology. Understanding these tissue context–dependent sex differences in the immune system is critical to deciphering the exact mechanisms that determine why women and men experience organ-specific infections, autoimmune or inflammatory diseases, and cancers differently. Only by parsing distinction at the tissue level can the development of personalized and precision immunotherapy approaches be conceived and then achieved.