Induction of antitumor immunity in mice by the combination of nanoparticle-based photothermolysis and anti-PD-1 checkpoint inhibition

Abstract

Generation of durable tumor-specific immune response without isolation and expansion of dendritic cells or T cells ex vivo remains a challenge. In this study, we investigated the impact of nanoparticle-mediated photothermolysis in combination with checkpoint inhibition on the induction of systemic antitumor immunity. Photothermolysis based on near-infrared light-absorbing copper sulfide nanoparticles and 15-ns laser pulses combined with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) increased tumor infiltration by antigen-presenting cells and CD8-positive T lymphocytes in the B16-OVA mouse model. Moreover, combined photothermolysis, polymeric conjugate of the Toll-like receptor 9 agonist CpG, and αPD-1 significantly prolonged mouse survival after re-inoculation of tumor cells at a distant site compared to individual treatments alone in the poorly immunogenic syngeneic ID8-ip1-Luc ovarian tumor model. Thus, photothermolysis is a promising interventional technique that synergizes with Toll-like receptor 9 agonists and immune checkpoint inhibitors to enhance the abscopal effect in tumors.

Keywords: Abscopal effect; Checkpoint inhibitor; CuS nanoparticle; Photothermolysis; Pulsed laser.