Host immunity following near-infrared photoimmunotherapy is enhanced with PD-1 checkpoint blockade to eradicate established antigenic tumors

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) induces responses correlated with shared tumor antigen expression, immunogenic cell death but has mostly failed to induce suggesting that antigenicity is a major determinant of durable antitumor responses in syngenic tumor mouse response to combination NIR-PIT and PD-1 blockade. models. We hypothesized that adaptive immune resistance Combination treatment induced complete rejection of could be limiting durable responses after treatmemt with MC38 tumors treated with NIR-PIT, as well as untreated, NIR-PIT. We investigated the effects of combining NIR-PIT distant tumors. Accordingly, tumor antigen–specific T-cell targeting cell-surface CD44 and PD-1 blockade in multiple responses were measured in both treated and untreated syngeneic tumor models. In two of three models, NIR-PIT tumors, validating the development of systemic antitumor monotherapy halted tumor growth, enhanced dendritic cell immunity. Mice that cleared tumors resisted subsequent tumor infiltration, and induced de novo tumor antigen–tumor challenge, indicating the presence of systemic specific T-cell responses absent at baseline. The addition immune memory. Cumulatively, these results demonstrate of PD-1 blockade reversed adaptive immune resistance, reversal of adaptive immune resistance following induction resulting in both enhanced preexisting tumor antigen–of innate and adaptive immunity by NIR-PIT, resulting in specific T-cell responses and enhanced de novo T-cell high rates of tumor rejection and/or significant tumor responses induced by NIR-PIT. Enhanced immune growth control in antigenic syngeneic models of cancer.