Science Paper Examines Factors to Identify Metastatic Prostate Cancer Responsive to Checkpoint Inhibitors

A high density of CD8 T cells, along with increased activity of a specific immune pathway, may help identify which metastatic prostate cancer patients will respond to immune checkpoint blockade (ICB) therapy, according to a report appearing in Science Translational Medicine. ICB has shown promise in treating advanced cancers but tends to be most effective against tumors with high mutational burden since there are neoantigens available for targeting by reinvigorated T cells. Still, data suggest that some patients with castration-resistant prostate cancer (CRPC) — a low mutational burden cancer — respond well to the checkpoint inhibitor ipilimumab. To better understand this, researchers from the University of Texas MD Anderson Cancer Center examined 30 CRPC patients receiving the drug in a clinical study, identifying a group of nine that had favorable responses to treatment and a group of 10 who had unfavorable responses. RNA sequencing revealed that the responsive patients had a higher density of CD8 T cells within tumors, as well as a gene signature indicating an IFN-gamma response. The findings, the study's authors write, indicate that certain patients may benefit from ICB despite low mutational burden and that pretreatment tissue correlatives such as CD8 T cells and IFN-gamma response gene signature may improve patient selection for treatment with ICB.