David A. Braun, MD, PhD, discusses the enrichment of SLAMF7-positive, CD8-positive T-cells and their role on nivolumab resistance in clear cell and non–clear cell renal cell carcinoma.
David A. Braun, MD, PhD, assistant professor of Medicine (Medical Oncology), Louis Goodman and Alfred Gilman Yale Scholar, Yale Cancer Center and Smilow Cancer Hospital, Yale School of Medicine, discusses the enrichment of SLAMF7-positive, CD8-positive T-cells and their role on nivolumab (Opdivo) resistance in clear cell and non–clear cell renal cell carcinoma (RCC).
Within many tumor types, T cells are the main effector cells and the main mediator of effective anti-tumor immunity, Braun begins. When checkpoint inhibitors work, they are mediated through T cells designed to specifically recognize and effectively kill tumor cells, Braun adds. With this is mind, investigators saw different outcomes from prior studies with single-cell RNA sequencing across disease settings, Braun says.
In this investigation, investigators observed 2 patterns of T cells. One pattern showed T cell that traveled toward a previously observed terminal exhaustion, and the other was a state that had not been characterized before, Braun explains. These T cells still expressed some dysfunction markers, but other markers were observed that were not expected, as well as slightly higher levels of cytotoxicity.
The question derived from this surprising finding was if these T-cell populations have an effect on patient outcomes. Investigators found that those whose disease was dysfunctional and exhaustive, having a lot of those cells didn't make any difference and it didn't have any impact on response or survival. However, when SLAMF7-positive, CD8-positive T-cells were enriched, that's where investigators saw clinical impact. Patients who had a high proportion of SLAMF7-positive T-cells had much worse outcomes, Braun emphasizes.
These patients had higher rates of progressive disease, worse progression-free survival, and a trend toward worse overall survival, Braun concludes.