Anti-PD-1 antibody-activated Th17 cells subvert re-invigoration of antitumor cytotoxic T-lymphocytes via myeloid cell-derived COX-2/PGE.

Anti-PD-1 antibody-mediated activation of type 17 T-cells undermines checkpoint inhibitor therapy in the LSL-Kras murine lung cancer model. Herein, we establish that the Th17 subset is the primary driver of resistance to therapy demonstrate that the ontogeny of dysplasia-associated Th17 cells is driven by microbiota-conditioned macrophages; and identify the IL-17-COX-2-PGE axis as the mediator of CD8 cytotoxic T-lymphocyte de-sensitization to checkpoint inhibitor therapy. Specifically, anti-PD-1 treatment of LSL-Kras mice, in which CD4 T-cells were deficient for RORc, resulted in a 60% increase in CTL cytotoxicity and a 2.