Sex-Related Differences in Immunotherapy Toxicities: Insights into Dimorphic Responses

Significant sex-based differences exist in the immune system and antitumor immune responses, potentially leading to variations in both the efficacy and toxicity of anticancer immunotherapies. Women generally mount stronger innate and adaptive immune responses than men, which can result in more severe immune-related adverse events (irAEs) during treatments with immune checkpoint inhibitors (ICIs). However, the importance of sex dimorphism in the safety of cancer immunotherapy remains underexplored in clinical oncology, despite its profound implications for treatment outcomes. Our review highlights the critical influence of biological sex on pharmacokinetics, pharmacodynamics, and immune responses, shaping ICI efficacy and the prevalence, type, and severity of irAEs. Integrating sex as a critical variable in cancer treatment and clinical trial design is essential for personalizing therapeutic strategies, bridging existing knowledge gaps, and enhancing survival rates and quality of life for patients across genders.