Sex‑biased immunity: the hidden variable in immuno‑oncology

The ability of an individual's immune system to mount a productive response against the tumor is critical for the success of immunotherapy. Clinical trials in multiple tumor types have revealed that the degree and way in which any one person's immune system mobilizes to eliminate tumor cells can vary widely, contributing to immunotherapeutic efficacy. Efforts to uncover biological factors contributing to response rates is a crucial area of ongoing research given the pressing clinical need to better stratify patients based on likelihood of response to a given therapy. While sex differences have long been observed in the field of immunobiology, the consideration of sex as a biological variable in the immunotherapeutic treatment of cancer patients has yet to be addressed or incorporated into patient care. Over the past decade, in part due to the National Institute of Health (NIH)‑mandated changes in how sex is handled as a biological variable, research has shifted markedly in how clinical and preclinical data are reported and interpreted. These changes have brought renewed attention to the ways sex shapes anti‑tumor immunity and responses to immunotherapy. In this review, we examine the expanding body of research demonstrating that male and female immune responses differ in their effectiveness against tumors and explore the implications of these differences for responses to immunotherapy.