Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer.

ABSTRACT: Colorectal cancer is the second leading cause of cancer mortality in the United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful in treating a subset of patients with colorectal cancer, the response rates remain low. We have found that riluzole, a well-tolerated FDA-approved oral medicine for treating amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth of colon cancer cells in syngeneic immune-competent mice. Riluzole-mediated tumor suppression was dependent on the presence of CD8+ T cells. Riluzole activates the cytosolic DNA sensing cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in colon cancer cells, resulting in increased expression of IFNβ and IFNβ-regulated ge

SUBMITTER: Liang B 

PROVIDER: S-EPMC11695182 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature