Aryl Hydrocarbon Receptor Signaling Controls CD155 Expression on Macrophages and Mediates Tumor Immunosuppression.

Journal Article (Journal Article)

Crosstalk between costimulatory and coinhibitory ligands are a prominent node of immune cell regulation. Mounting evidence points toward a critical role for CD155, the poliovirus receptor, in suppressing T cell function, particularly in cancer. However, relative to other known costimulatory/coinhibitory ligands (e.g., CD86, CD80, PD-L1), the physiological functions of CD155 and the mechanisms controlling its expression remain unclear. We discovered that CD155 expression is coregulated with PD-L1 on tumor-associated macrophages, is transcriptionally regulated by persistently active aryl hydrocarbon receptor (AhR), and can be targeted for suppression via AhR inhibition in vivo. Therapeutic inhibition of AhR reversed tumor immunosuppression in an immune competent murine tumor model, and markers of AhR activity were highly correlated with tumor-associated macrophage markers in human glioblastomas. Thus, CD155 functions within a broader, AhR-controlled macrophage activation phenotype that can be targeted to reverse tumor immunosuppression.

Full Text

Duke Authors

Cited Authors

  • McKay, ZP; Brown, MC; Gromeier, M

Published Date

  • March 15, 2021

Published In

Volume / Issue

  • 206 / 6

Start / End Page

  • 1385 - 1394

PubMed ID

  • 33504618

Pubmed Central ID

  • PMC7946722

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.2000792


  • eng

Conference Location

  • United States