Human metastatic melanoma cells, courtesy of the Web site of the National Cancer Institute (http://www.cancer.gov).
The abundance of a subtype of white blood cells in melanoma tumors can predict whether or not patients will respond to a form of cancer immunotherapy known as checkpoint blockade, according to a new study led by UC San Francisco researchers and physicians. The research offers the beginnings of a solution to a puzzle that has vexed oncologists: Though many patients with previously untreatable cancers are in remission after receiving checkpoint-blockade drugs, only about 20 percent of patients who receive them respond.
UCSF’s Michael Rosenblum, MD, PhD, assistant professor of dermatology and senior author of the new study, said that the new work has generated insights that may help bring the benefits of checkpoint inhibitors to a greater number of patients. Though the study was done in melanoma patients, Rosenblum said that the findings should apply to other types of cancer as well.
As reported online in the August 15, 2016 issue of the Journal of Clinical Investigation, the research team analyzed tumors from 40 patients, and found that the relative size of a population of T cells known as partially exhausted CD8+ cells in the tumors accurately predicted most patients' responses to immunotherapy drugs that target a protein called PD-1. If 30 percent or more of the immune cells in a given patient’s tumor before treatment were of the proper subtype, that patient responded to therapy; if fewer than 20 percent were such cells, there was no response.
Intriguingly, the CD8+ cells that predicted response to anti-PD-1 therapy expressed high levels of PD-1 and also of CTLA-4, another well-known immune checkpoint protein targeted by immunotherapy drugs. The cells are called “partially exhausted” because they can't produce certain cytokines, signaling molecules that regulate the body's immune response, and as a result aren't able to adequately respond to antigens present in tumors.