Acquired resistance to PD-L1 inhibition enhances a type I IFN-regulated secretory program in tumors

ABSTRACT: Therapeutic inhibition of programmed cell death ligand (PD-L1) is linked to alterations in IFN signaling. Since IFN-regulated intracellular signaling can control extracellular secretory programs in tumors to modulate immunity, we examined IFN-related secretory changes in tumor cells following resistance to PD-L1 inhibition. Here we report an anti-PD-L1 treatment-induced secretome (PTIS) in tumor models of acquired resistance that is regulated by type I IFNs. These secretory changes can suppress activation of T cells ex vivo while diminishing tumor cell cytotoxicity, revealing that tumor-intrinsic treatment adaptations can exert broad tumor-extrinsic effects. When reimplanted in vivo, resistant tumor growth can slow or stop when PTIS components are disrupted individually, or when type I IFN

SUBMITTER: Dr. Yuhao Shi 

PROVIDER: S-SCDT-10_1038-S44319-024-00333-0 | biostudies-other |

REPOSITORIES: biostudies-other