Abstract A31: Reprogramming of tumor-associated macrophages by anti-Program Death Ligand 1 (PDL1)

Abstract

Tumor-associated macrophages play a vital role in shaping tumor environment and contribute to the cancer-immune set point. Immunotherapy such as aPD1/aPDL1 has demonstrated remarkable therapeutic efficacy on a variety of cancers through reinvigorating CD8+ T cells. However, its impact on macrophages largely remains unclear. Here by using mouse MC38 cancer model, we show that aPDL1 re-programs macrophages from M2-like to M1-like: it decreases Arginase-I (ARG1), an M2-like marker, and increases iNOS and MHCII, both M1-like markers, on macrophages. Next, we investigate the mechanism behind the reprogramming. We identify that IFNg from CD8+ T cells and NK cells is boosted by aPDL1 and is required for macrophage re-polarization. IFNg blockade abrogates this process. Finally, we examine additional cancer models and observe similar phenotypes in another aPDL1-responsive model, but not in a third, non-responsive model. We conclude that tumor associated macrophage is re-programmed from M2-like to M1-like following aPDL1 treatment, and that it is mediated by enhanced IFNg in the tumor environment. Our findings suggest macrophage reprogramming as a novel mechanism and an independent avenue to promote antitumor activity via modulation of the cancer-immune set point. Citation Format: Huizhong Xiong, Marina Moskalenko, Ryan Rodriguez, Stephanie Mittman, Michelle Yang, Jeong Kim, Rafael Cubas Barcelli. Reprogramming of tumor-associated macrophages by anti-Program Death Ligand 1 (PDL1) [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A31.