Recent clinical data highlights the importance of immune cell localization, phenotype, and gene signature as it correlates to a productive anti-tumor response. Preclinically, multiple syngeneic mouse models have been used to study the effects of immunomodulation and define anti-tumor responses to transplanted “self” tumors. However, while the literature describes distinct aspects of many of these models, there is no comprehensive dataset comparing and contrasting their tumor-immune microenvironments across models. These data are critical for better understanding the role that various immune populations play in the anti-tumor response and interpreting observed changes in tumor clearance following treatment with immunomodulatory agents. We have therefore established a platform that 1) quantitates the types of immune cells within murine tumor models, and 2) describes the location of these cells within the tumor. In parallel to the immunophenotyping efforts we have benchmarked tumor models based on their response to antibodies against T cell checkpoint pathways.
We sought to use this immunophenotyping platform to identify specific immune modulation that occurs in syngeneic tumors post depletion of macrophages via CSF1R blockade. Tumor-associated macrophages (TAMs) are believed to help promote tumor survival through suppression of the adaptive immune response and the secretion of growth factors that promote tumor growth and angiogenesis. Therefore depletion of TAMs should lead to T-cell recruitment and bolster the antitumor T-cell response. Here we show that treatment of CT-26 and RENCA syngeneic tumors with a CSF1R antagonist leads to depletion of MHCII+ and F4/80+ expressing cells. Future experiments will seek to understand if CSF1R blockade improves the response to T-cell checkpoint immunotherapies. In summary, the development of a murine tumor immunophenotyping platform has allowed insight and evaluation of immune cells in the tumor microenvironment that can ultimately be leveraged to understand the synergistic effects of immunotherapeutics.
Citation Format: Brian Belmontes, Stephanie Matyas, Sarah O’Brien, Hong Tan, Kenneth Ganley, Kimberly Merriam, Jim Rottman, Jackson Egen, Pedro Beltran, Gordon Moody. Developmentof a murine tumor immunophenotyping platform to support drug discovery anddevelopment in immuno-oncology. [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 4038.