▎ WuXi AppTec content team editor
Due to the different levels of hormones in men and women, there will be some differences in immune function. This difference may manifest itself in different aspects such as metabolism and disease progression. Especially in the field of cancer, there has always been a special phenomenon that in non-reproductive cancers, many data will still have gender differences.
For example, bladder cancer or liver cancer, there are some differences in the incidence of male and female disease progression and the degree of response to treatment. In most cases, male cancer patients have worse prognosis and treatment outcomes, which has long been a mystery in the scientific community.
Recently, a study in Science Immunology conducted a sex-specific study of non-reproductive cancer types, analyzing differences in tumor immune responses in men and women. Studies have found that differences in T cell function are the direct cause of sex differences in tumor progression.
The study focused on CD8+ T cells, which are the main population of active immune cells that attack cancer cells, are able to mediate adaptive immunity and produce anti-tumor responses.
Image credit: 123RF
CD8+ T cells are highly resistant to cancer, but they are easily exhausted due to their constant exposure to antigenic stimulation in the tumor microenviron, which is why the immune system loses sustainability in the process of fighting cancer.
Although the loss of T cell function is the most direct surface cause, according to the new study, androgen is likely to be the real affecting molecule because it is directly involved in the process of failure of CD8+ T cells.
The study samples analyzed human and mouse cancer samples by sex, and the results showed that CD8+ T cells from the male side showed more features of weakened anti-tumor function, and these T cells were more likely to fail.
▲The study is based on experiments on CD8+ T cells, revealing differences in the immune response of tumors of both sexes (Image source: References[1])
Androgens mainly affect T cell function by regulating a protein called TCF1, a powerful class of T cell regulatory molecules that, under the constant stimulation of androgens, will gradually differentiate T cells in the direction of failure, producing more precursor cells of failing T cells.
After artificially blocking androgen receptors in mice, the researchers found that T cells in the tumor microenvironment improved their survival, performed better functions, and differentiated in the direction of effector T cells, rather than the failing T cells of the past. In addition, after androgen receptors are blocked, anti-PD-1 immunosuppressants can exert a more efficient tumor clearance effect.
Studies have shown that androgen-mediated CD8+ T cell dysfunction can cause tumors to grow faster, thus leading to worsening treatment outcomes. Targeting such signaling pathways and altering subsequent cascades may improve the effectiveness of cancer immunotherapy.
Resources:
[1] Study reveals male sex hormones are new targets for cancer immunotherapy. Retrieved Apr 18th, 2022 from https://medicalxpress.com/news/2022-04-reveals-male-sex-hormones-cancer.html
[2] Hyunwoo Kwon et al, Androgen conspires with the CD8 + T cell exhaustion program and contributes to sex bias in cancer, Science Immunology (2022). DOI: 10.1126/sciimmunol.abq2630
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