| First Author | Yang C | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 7 | Pages | 1268-1283.e9 |
| PubMed ID | 35700739 | Mgi Jnum | J:326623 |
| Mgi Id | MGI:7316260 | Doi | 10.1016/j.immuni.2022.05.012 |
| Citation | Yang C, et al. (2022) Androgen receptor-mediated CD8(+) T cell stemness programs drive sex differences in antitumor immunity. Immunity 55(7):1268-1283.e9 |
| abstractText | The incidence and mortality rates of many non-reproductive human cancers are generally higher in males than in females. However, the immunological mechanism underlying sexual differences in cancers remains elusive. Here, we demonstrated that sex-related differences in tumor burden depended on adaptive immunity. Male CD8(+) T cells exhibited impaired effector and stem cell-like properties compared with female CD8(+) T cells. Mechanistically, androgen receptor inhibited the activity and stemness of male tumor-infiltrating CD8(+) T cells by regulating epigenetic and transcriptional differentiation programs. Castration combined with anti-PD-L1 treatment synergistically restricted tumor growth in male mice. In humans, fewer male CD8(+) T cells maintained a stem cell-like memory state compared with female counterparts. Moreover, AR expression correlated with tumor-infiltrating CD8(+) T cell exhaustion in cancer patients. Our findings reveal sex-biased CD8(+) T cell stemness programs in cancer progression and in the responses to cancer immunotherapy, providing insights into the development of sex-based immunotherapeutic strategies for cancer treatment. |
