Abstract 1221: Mitomycin C induces programed cell death ligand 1 overexpression but enhances anticancer immunity in none small cell lung cancer

Abstract Blockade of the checkpoint inhibitor programmed death 1 ligand (PDL1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are progressive with low response rate. To enhance the efficacy of PDL1 blockade immunotherapies, we tried to combine chemotherapy capable of enhancing antitumor immunity. Here, we screened that tumor cells with MMC pre-treatment was significantly killed by co-cultured lymphocytes than without ones. Indeed, tumor cells treated with MMC showed the increased release of granzyme B and TNF-α. And tumor lysis was enhanced by combined with PD1 Ab in vitro. Mice treated with both anti-PDL1 and MMC showed an improved overall survival and inhibition within the tumor, indicating that this combination improves the overall quality of the immune response generated. Mechanically, MMC was observed to upregulate PDL1 expression in a concentration and time manner. MMC activated c-JUN to bind with PDL1 promoter and recruited its co-factor, STAT3 to accelerate PDL1 expression. MMC induced an IFN-γ independent signature within the tumor cell, and ERK signaling pathway was activated. A reason for its enhancement in antitumor immunity was the high expression of MHC-I after MMC treatment which attracted more CD8+ T cells. These findings identified a potential mechanism for the observed benefit of combining MMC and PDL1 blockade, in which MMC induces PDL1 upregulation and MCH-I high expression, thereby converting the tumor cell into an immunogenic one, when block PDL1, the antitumor response was enhanced. Citation Format: Min Luo. Mitomycin C induces programed cell death ligand 1 overexpression but enhances anticancer immunity in none small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1221.