Fractional Laser Treatment Boosts Systemic Anti-Tumor Immunity in Combination with OX40 Agonist and PD-1 Blockade

Abstract

While ablative fractional photothermolysis (aFP) with a 10,600 nm CO2 laser is employed for a wide variety of dermatologic conditions, its applications in oncology are relatively unexplored. Building off our previous work, we investigated the effect of unilateral aFP treatment in combination with anti-PD-1 blocking antibody and OX40 agonist on bilateral tumor growth and remission. A CT26 wild type (CT26WT) colon carcinoma cell line was established bilaterally on the hind flanks of a standardized mouse model and tumor characteristics were investigated on aFP treated and untreated sides. Remarkably, triple therapy with fractional CO2 laser in combination with anti-PD-1 antibodies and OX40 agonists resulted in significantly slower tumor growth and complete remissions on bilateral tumors. Flow cytometric analysis showed the triple treatments elicited an increase of granzyme B+ CD8+T cells due to synergistic effect of aFP treatment and the checkpoint molecules, including the induction of CD103+ CCR7+ dendritic cells (DCs) in aFP-treated tumor by aFP treatment, XCR1+ DCs in drainage lymph node by anti-PD-1 inhibitor and OX40+ Ki67+ CD8+ T cells in the lymph node by OX40 agonist. Triple therapy-mediated tumor regression and survival was abrogated upon CD8+ T cell depletion. Importantly, when two mismatched cancer cells were implanted into mice, the effect of the triple therapy on distant tumor was abrogated, showing antigen specificity of the T cell immunity induced by triple therapy. This study highlights the efficacy of aFP a novel adjuvant for current cancer immunotherapeutics.