Abstract 4898: Effects of chemotherapeutic agents on the tumor immune microenvironment

Immunotherapeutic agents have shown dramatic success in oncology in recent years and several have been approved in melanoma and lung cancer. One strategy for extending the benefit of immunotherapy is to evaluate these agents in combination with standard of care chemotherapy, with the goal of bringing the benefit of immunotherapy into earlier lines of treatment. We have carried out a systematic evaluation of the effects of different classes of chemotherapeutic agents (including alkylating agents, platinum based agents, and taxanes) on the tumor immune microenvironment of syngeneic murine tumor models (CT26 and MC38) in two different strains of mice (BALB/c and C57BL/6). We found that different chemotherapeutic agents caused markedly different changes in the composition and cell phenotype of the tumor immune environment. The majority of chemotherapeutic agents resulted in a mild to moderate increase in CD8+ T cells in the tumor. Some agents also altered the activation state of these CD8+ cells as measured by the level of PD-1 and IFN-gamma. A subset of the chemotherapeutic agents resulted in profound changes in the number of CD4+ cells, including regulatory T cells, as well as changes in myeloid subpopulations including monocytes, neutrophils, and macrophages. In addition to single agents studies, we carried out combination studies of selected chemo agents with simultaneous addition of anti-PD-L1. Several of these combinations caused pronounced increases in efficacy above single agent treatment. We will present the combination pharmacodynamic marker changes and efficacy of these treatments. Our findings demonstrate that chemotherapeutic agents can stimulate the tumor immune environment, at least transiently, through multiple mechanisms. Different subsets of chemotherapeutic agents display unique changes in the tumor immune infiltrate, and may require different immunotherapeutic approaches. These findings provide a rationale for testing immunotherapy-chemotherapy combinations in the clinic. Citation Format: Marcia P. Belvin, Shiuh-Ming Luoh, Jeanne Cheung, Erin McNamara, Rafael Cubas, Jeong Kim. Effects of chemotherapeutic agents on the tumor immune microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4898.