Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8⁺ T cell exhaustion.

ABSTRACT: Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic and RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated collagen correlates with decreased total CD8⁺ T cells and increased exhausted CD8⁺ T cell subpopulations in murine and human lung tumors. Collagen-induced T cell exhaustion occurs through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1. Reduction in tumor collagen deposition through LOXL2 suppression increases T cell infiltration, diminishes exhausted T cells, and abrogates resistance to anti-PD-L1. Abrogating LAIR1 immunosuppression through LAIR2 overexpression o

SUBMITTER: Peng DH 

PROVIDER: S-EPMC7481212 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature