New targets for immunotherapy in male cancer patients: Sex hormones
on April 16, and led by researchers at the Pelotonia Cancer-Immune Institute (PIIO) at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and the Richard Research Institute J. Solove (OSUCCC – James) examined differences in intracompartmental immune responses between male and female non-reproductive cancers.
The focus of this study is on the T-cell immune response to the primary malignancy determinant of cancer outcomes and the key target that has contributed to the renaissance of cancer immunotherapy. seen in recent years. This study makes an important finding illustrating how male sex hormones contribute to cancer-related sex dependence through regulation of CD8+ T cells – some of the cells known as CD8+ T cells. cancer “killer” cells, mediate adaptations and are important for proliferation.
Lead author of the study, Dr. Zihai Li, cancer immunologist, oncologist and founding director of PIIO at OSUCCC – James said,Collectively, these findings highlight the promotion of androgen-mediated CD8+ T-cell dysfunction in cancer and suggest broader implications for the development of therapies to address disparities. gender in health and disease.”
T cells in men
Androgens are sex hormones present in more men than in women and can therefore contribute to immunosuppression in men as well as in women. Androgens include testosterone and dihydrotestosterone – inhibitory coreceptors that are more strongly activated on CD8+ T cells. This function was observed in both men and in mice. This study shows that cancer-free CD8+ T cells in male subjects, including both human and mouse patients, are more likely to have features of impaired anti-tumor immune function, also known as “exhausted” T cells. Androgen signaling promotes the depleted ancestral CD8+ T cell phenotype through regulation of the expression of TCF1, a key regulator of CD8+ T cell function.
Professor Li of Ohio State University School of Medicine said, “Androgen-mediated promotion of CD8+ cell dysfunction leads to faster tumor growth and worsening outcomes, and targeting this signaling cascade holds an important key to ameliorating the Current cancer immunotherapy.“
This work was made possible through a unique partnership that occurred at the Ohio State Pelotonia Cancer-Immunology Institute. PIIO was founded in 2019 and is a comprehensive research initiative focused on harnessing the body’s immune system to fight cancer at all levels – from prevention to treatment and survive.
PIIO was established through a $102 million commitment from OSUCCC – James and Pelotonia. Pelotonia was founded in 2008 and it was founded with the goal of funding innovative cancer research, and has raised more than $236 million for cancer research.
Additional financial support for the study came from the National Institutes of Health, the Prostate Cancer Foundation, the Canadian Institutes of Health Research, and the Hollings Cancer Center.
Other study authors include Hyunwoo Kwon, Johanna Schafer, No-Joon Song, Satoski Kaneko, Anqi Li, Tong Xiao, Anjun Ma, Carter Allen, Komal Das, Lei Zhou, Brian Riesenberg, Yuzhou Chang, Payton Weltge, Maria Velegraki, David Oh, Lawrence Fong, Qin Ma, and Debasish Sundi, as well as their respective co-authors Drs. Xue Li (Cedars-Sinai Medical Center) and Dongjun Chung (OSUCCC – James).