The effect of patient sex on the efficacy and safety of anticancer immunotherapy

Abstract

ABSTRACT Introduction: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with several types of cancer. A sex-based dimorphism in efficacy and toxicity of chemotherapies is well known and was recently described for anticancer immunotherapy. Areas covered: This review presents an overview of existing biological differences between males and females, including the immune system dimorphism, which represent the rationale for a sexual dimorphism in activity and toxicity of anticancer immunotherapies. Expert opinion: Clinical and preclinical research focused its efforts on the characterization of cancer molecular background and the complexity of tumoral microenvironment. Host factors, such as sex of a patient, and their potential roles in modulating cancer behavior as well as sensitivity and toxicity to anticancer treatments have been under-evaluated and poorly studied. Differences between males and females have been reported in studies with chemotherapy, both in activity and toxicity. Sex-based dimorphism is well known and relies on a complex interplay between immune functions, hormones, genes, and microbioma. With the extensive use of new drugs such as ICIs that lead to an immune system activation, the role of sex in modulating responses and immune-related toxicities needs to be taken into account to further tailor therapeutic approaches for males and females.