Cancer Research | 2019
Abstract 2803: CSF-1 receptor-mediated macrophage depletion can induce immunomodulatory resistance mechanisms in murine tumor models
Abstract
Tumor associated macrophages (TAMs) are present within the stroma of most solid tumors where they can act to inhibit immune responses and promote disease progression through expression of immunosuppressive factors and modulation of tumor stroma. Tumor immunotherapies aimed at depletion of TAMs, for instance through the use of blocking antibodies against the CSF1 receptor (CSF1R), have been widely explored, with multiple studies demonstrating that blocking TAM function can inhibit tumor growth/metastasis and stimulate anti-tumor immunity. In order to further dissect the functions of TAM populations and define conditions under which antiCSF1R immunotherapy may have benefit, we evaluated the effect of antiCSF1R treatment on multiple subcutaneous murine tumor models with varying dosing parameters. Despite robust macrophage depletion, some tumor models, such as Renca renal cell adenocarcinoma, showed only a modest change in tumor volume and minimal effector T cell recruitment or activation in response to anti-CSF1R therapy. Comprehensive flow cytometry-based immunophenotyping and single-cell RNA sequencing on immune cells isolated from antiCSF1R and isotype control-treated Renca tumors revealed shifts in gene expression patterns related to vascular remodeling, hypoxic responses, and enhanced regulatory T cell activity. These studies indicate macrophage depletion may, under some conditions, result in compensatory anti-tumor immune responses that could limit the clinical benefit of this therapeutic approach. Citation Format: Sarah A. O9Brien, Katarzyna Skrzypczynska, Jessica Orf, Brian Belmontes, Hong Tan, Daniel Lu, Ian Driver, Jackson Egen. CSF-1 receptor-mediated macrophage depletion can induce immunomodulatory resistance mechanisms in murine tumor models [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 2803.