Sex Disparities in Cancer Immunotherapy: A Review

Mpora Kakwanzi Evelyn

Department of Pharmacognosy Kampala International University Uganda

 Email: evelyne.mpora@studwc.kiu.ac.ug

ABSTRACT

Cancer immunotherapy has revolutionized cancer treatment, particularly through immune checkpoint inhibitors (ICIs) targeting proteins like PD-1, PD-L1, and CTLA-4. While these therapies have shown significant survival benefits across various cancers, sex-based disparities in treatment response and outcomes have emerged. This review explores the mechanisms behind these differences, focusing on genetic, hormonal, and immune system variations between male and female patients. Women tend to exhibit stronger immune responses due to the presence of two X chromosomes and the immunostimulatory effects of estrogen, which enhances immune activity. Conversely, men’s single X chromosome and the immunosuppressive effects of testosterone contribute to a less vigorous immune response. These biological differences manifest in clinical outcomes, with men generally experiencing better overall survival rates from ICIs, while women are more prone to immune-related adverse events (irAEs), including autoimmune toxicities. However, in certain cases, women may demonstrate more robust long-term survival benefits from treatments such as CTLA-4 inhibitors, despite higher toxicity risks. Beyond ICIs, sex disparities also extend to adoptive cell therapies (ACT) and cancer vaccines, where female patients often display stronger immune responses but face increased risks of side effects, necessitating personalized approaches to therapy. The review also discusses emerging research on the tumor microenvironment (TME), gut microbiome, and sex-specific pharmacokinetics and pharmacodynamics as contributing factors to these disparities. Understanding these mechanisms is critical for improving cancer immunotherapy outcomes for both sexes. Future research should focus on investigating the role of sex hormones, the microbiome, and developing biomarkers to better predict responses to immunotherapy. Clinically, the findings highlight the need for tailored treatment strategies that account for sex-specific differences, aiming for more equitable and effective cancer care.

Keywords: Cancer immunotherapy, Immune checkpoint inhibitors (ICIs), Sex-based disparities, PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors

CITE AS: Mpora Kakwanzi Evelyn. (2024). Sex Disparities in Cancer Immunotherapy: A Review. Research Output Journal of Public Health and Medicine 4(1):19-24. https://doi.org/10.59298/ROJPHM/2024/411924