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Soo Park, MD
Soo Park, MD
Posted: Monday, December 23, 2024
For patients with advanced cutaneous melanoma, KIR-positive, CD8-positive regulatory T cells may serve as a potential circulating biomarker and therapeutic target, according to research published recently in Nature Immunology. Additional investigative efforts focused on their role in the tumor microenvironment and as cellular mediators of immune evasion in human cancer are warranted to help guide the development of therapeutic strategies, explained senior author David A. Hafler, MD, FANA, of Yale School of Medicine, New Haven, Connecticut, and colleagues.
“These novel investigations extend the role of these newly discovered suppressor cells, and their association with worse overall survival of patients with cancer provides a potential new immunotherapeutic approach by targeting these cells,” commented Dr. Hafler in an institutional press release.
A total of 17 patients with immunotherapy-naive cutaneous melanoma were recruited for the study. Histologically confirmed tumor tissue and blood samples were obtained from patients. Samples were subjected to an array of biomolecular assays, including small cytoplasmic RNA sequencing, immunophenotyping, next-generation sequencing, and flow cytometry.
The study findings revealed a subpopulation of CD8-positive T cells that resemble KIR-positive, CD8-positive regulatory T cells and target other tumor antigen–reactive KIR-positive, CD8-positive regulatory T cells. In addition, there is a significant correlation between the frequency of KIR-positive, CD8-positive regulatory T cells in the tumor and blood. These findings suggest that blood levels of KIR-positive, CD8-positive regulatory T cells may be used to estimate the number of T cells in the tumor. Furthermore, a decreased 3-year overall survival was identified in patients with elevated levels of KIR-positive, CD8-positive regulatory T cells.
The study authors also emphasized the importance of testing for CD8-positive regulatory T cells in patients’ blood to help determine who might benefit from current and future cancer therapies. “We actually find this CD8-positive T-cell subpopulation in everyone—it’s just a matter of what proportion we see in the blood,” commented first author Benjamin Y. Lu, MD, PhD, of Yale Cancer Center. “We know that as we get older, the number of CD8-positive regulatory T cells tends to go up. They also tend to go up when there’s an active infection or inflammation.”
Disclosure: For full disclosures of the study authors, visit nature.com.
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