A Barbara Ann Karmanos Cancer Institute and Wayne State University (WSU) School of Medicine researcher has discovered that blocking the production of a specific type of T cell safely impairs tumor growth in prostate cancer and melanoma. The finding identifies a viable target to safely enhance anti-cancer immunity.
“Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a non-redundant manner,” was published in August 2024 in the Proceedings of the National Academy of Sciences, a peer-reviewed journal of the National Academy of Sciences. Eric Sebzda, Ph.D., associate professor of Biochemistry, Microbiology and Immunology, and member of the Tumor Biology and Microenvironment (TBM) Research Program at Karmanos, and his colleagues detailed findings in the report that demonstrates blocking the production of peripheral Tregs, a type of T cell, safely inhibits tumor growth in preclinical models of these two cancers.
The design of new cancer therapies hinges upon the identification of tumor-mediated mechanisms that impair immunity, Dr. Sebzda said. Regulatory T cells, or Tregs, are a key component of cancer-derived immune suppression, but these cells are necessary to prevent systemic autoimmunity, so direct targeting of Tregs is not a clinical option for cancer patients. However, eliminating the production of pTregs, a subset of Tregs necessary for melanoma and prostate cancer progression, safely prevented malignancy in animal models.
“Our results indicate that tumor-specific pTregs are critical for early stages of cancer progression and blocking the generation of these inhibitory lymphocytes safely delays or prevents malignancy in preclinical models of melanoma and prostate cancer,” Dr. Sebzda said. “Importantly, pTreg function is maintained between mice and humans, which strongly suggests that pTregs perform a similarly deleterious role in cancer patients.”
The elimination of pTregs, he noted, does not lead to overt pathology associated with autoimmunity. In fact, blocking the generation of pTregs in preclinical animal models actually improved immune responses correlated with positive cancer patient outcomes.
Researchers involved in this discovery include the following from Karmanos and WSU: Md Moazzem Hossain, research assistant; Paul King, research assistant; Justin Hackett, medical student; Herve Gerard, research assistant; Rajmund Niwinski, medical student; and TBM Research Program members Gregory Dyson, Ph.D., professor, and Heather Gibson, Ph.D., assistant professor. Additionally, Lan Wu, M.D., and Luc Van Kaer, Ph.D., of Vanderbilt University Medical Center; and Alexander Borowsky, M.D., of the University of California UC Davis also contributed to the research.
This study was supported by NIH NCI T32 grant CA009531 (Justin Hackett), the Elsa U. Pardee Foundation (Heather Gibson), the Center for Genomic Pathology at UC Davis (Alexander Borowsky), NCI U01CA196406 (Alexander Borowsky), DOD PCRP grant PC140122 (Eric Sebzda, Luc Van Kaer), NCI P30-CA022453 (Gregory Dyson, Eric Sebzda) and American Cancer Society grant DBG-23-103670-01-IBCD (Eric Sebzda). The Microscopy, Imaging and Cytometric Resources Core is supported by National Institutes of Health Center grants P30 CA22453 and R50 CA251068-01.
Originally published in Today@Wayne.