Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy

Immune checkpoint inhibitors, such as anti-PD-1 antibodies, represent a significant advancement in cancer immunotherapy, but their efficacy varies notably between individuals, influenced by complex biological systems. Recent evidence suggests that sex-related biological differences play a pivotal role in modulating these responses. This study uses a systems biology approach to examine how sex-specific differences in the immune system contribute to variability in the response to treatment. Our model extends previous frameworks by incorporating sex-specific parameters that reflect observed immunological distinctions. The results from the simulation studies align with our clinical observations, showing that on average, males exhibit a more robust response to anti-PD-1 treatment compared to females. Additionally, this study explores the potential of combination therapy with recombinant IL-12, revealing sex-specific differences in treatment efficacy. These findings underscore the need for personalized immunotherapy strategies that consider individual immunological profiles, including sex, to optimize treatment outcomes.