Sex Matters: Hormonal and Chromosomal Determinants of Autoimmunity and Anti‐Cancer Immunity Across the Lifespan

ABSTRACT Sex plays a key role in shaping both anti‐cancer immunity and autoimmunity. Biological factors underlying sexual dimorphism have now been identified in multiple aspects of anti‐cancer immunity and autoimmunity. These factors include sex differences in hormone levels, chromosome complement, and expression of the long non‐coding RNA XIST. In this review, we discuss recent advances delineating how these differences alter immune responses against cancer and autoimmune responses against healthy tissues. Moreover, we now understand that hormone levels change (e.g., in mini‐puberty, menopause, and andropause) and that somatic alterations in chromosomal complement accumulate (e.g., loss of Y LOY chromosome) across the lifespan. We also include here a discussion of how these changes affect anti‐cancer immunity and autoimmunity across a lifetime. These recent advances will set the stage for identifying immunotherapeutic approaches that optimize anti‐cancer immunity while controlling the autoimmune responses.