Abstract 5128: Characterization of tumor immune microenvironment in response to PD-L1 therapy initiated at different time points post inoculation in syngeneic mouse models

Abstract

Abstract The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, progression and responses to therapy. Cells and molecules of the immune system are fundamental components of the tumor microenvironment which have been known to vary widely and are important in determining the anti-tumor immune response. The approval of immune checkpoint inhibitors like PD-1 and CTLA-4 antibodies has resulted in a lot of research activity in immune-oncology. Syngeneic mouse models have been utilized to understand the preclinical immune response as a surrogate to the clinical response. The timing of immune checkpoint inhibitor dosing is supposed to play an important role on the tumor growth in mouse models. In order to understand the correlation of tumor regression, survival and immune response in a preclinical mouse model, we evaluated the effect of different times of treatment initiation with Program Death Ligand-1 (PD-L1) on tumor volume, survival and tumor infiltrating leukocytes (TIL’s). Various dosing regimens evaluated included initiation of PD-L1 therapy on the day of inoculation, 6 and 12 days post inoculation. Tumors were collected from three different syngeneic mouse models (CT26, RENCA and B16F10) and profiled for the presence of tumor infiltrating leukocytes (TIL’s) using flow cytometry. Major sub-population of TIL's examined included T-regulatory cells (Treg’s), Tumor Associated Macrophages (TAM’s) and Myeloid Derived Suppressor Cells (MDSC’s). Finally, an attempt was made to identify any correlation or lack thereof between tumor growth and tumor immune microenvironment. Citation Format: Geeta Sharma, Susan Wu, Robert Mihalek, Ann Fiore, Matthew Gale, Christa Dias, Wendy Grant, Nidia Hernandez. Characterization of tumor immune microenvironment in response to PD-L1 therapy initiated at different time points post inoculation in syngeneic mouse models. [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 5128.