Science Immunology: Why are men more prone to cancer and often have worse outcomes?

Patients with non-reproductive cancers, such as bladder and liver cancers, differ significantly in incidence, progression, response to treatment, and survival outcomes, depending on the sex of the patient

CD8+ T cells have great potential to eliminate malignant cells, and they kill tumor cells by recognizing different antigens, however, under continuous antigen stimulation, CD8+ T cells often lose their function in the tumor microenvironment, i.

T cell exhaustion in the tumor microenvironment may be affected by a variety of factors, such as regulatory T cells, inhibitory cytokines, immune checkpoint receptors and ligands, metabolism, etc.

On April 14, 2022, Li Zihai of Ohio State University and Li Xue of Harvard Medical School published a research paper titled: Androgen conspires with the CD8+ T cell exhaustion program and contributes to sex bias in cancer in the journal Science Immunology .

The study investigated differences in tumor immune responses between men and women in cancers of non-reproductive origin, finding and revealing that androgens promote CD8+ T cell depletion, which leads to faster tumor cell growth

This landmark discovery highlights the promoting role of androgen-mediated CD8+ T cell dysfunction in cancer, suggests a role for sex differences in health and disease, and provides a new direction for cancer immunotherapy

Overall, these findings highlight the promoting role of androgen-mediated CD8+ T cell dysfunction in cancer, with important implications for addressing gender disparities in cancer treatment, said the study's corresponding author, Professor Li Zihai from The Ohio State University.

Li Zihai (left), Li Xue (right)

Androgen is the most abundant sex hormone in males

Note: The Sry gene is a sex-determining gene located on the Y chromosome.

Next, the research team further revealed the mechanism behind it.

The research team also demonstrated that the use of androgen receptor inhibitors or androgen deprivation therapy (ADT) can significantly enhance the efficacy of PD-1 immune checkpoint inhibitors

Collectively, this study is the first to demonstrate for the first time that androgen signaling directly regulates Tcf7 and induces CD8+ T cell depletion, and that blocking the androgen receptor in CD8+ T cells alone allows male mice to perform as well as female mice Fights cancer and enhances the efficacy of PD-1 inhibitors

Original source:

HYUNWOO KWON, JOHANNA M.