The "Inside" Story on Tumor-Expressed PD-L1.

Journal Article (Editorial)

While the extracellular domain of PD-L1 is well-recognized for playing a critical role in immune evasion by suppressing CD8+ T-cell activity through direct PD-1 interactions, a series of studies has evolved highlighting important functional roles for the PD-L1 cytoplasmic domain in supporting various aspects of tumorigenesis. Kornepati and colleagues contribute to our overall understanding of PD-L1 in tumor biology by describing a link between tumor PD-L1 expression and DNA repair. These studies demonstrate that PD-L1 promotes breast cancer type 1 (BRCA1)-mediated homologous recombination while inhibiting cytosolic DNA sensing, thus suppressing tumor immunogenicity. Notably, these effects could not be reversed with anti-PD-L1 antibodies utilized in the clinic, suggesting that pharmacologic agents promoting PD-L1 degradation may be a more effective treatment strategy for select tumors. Studies that are improving our understanding of the pathways driven by PD-L1 cytoplasmic signaling are providing increased insight into the design of next generation combinatorial immunotherapy strategies. See related article by Kornepati et al., p. 2156.

Full Text

Duke Authors

Cited Authors

  • Hanks, BA

Published Date

  • June 6, 2022

Published In

Volume / Issue

  • 82 / 11

Start / End Page

  • 2069 - 2071

PubMed ID

  • 35661198

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-22-1060

Language

  • eng

Conference Location

  • United States