Abstract 5568: Understanding the role of immune exclusion in mammary tumor growth

Abstract

Abstract Multiple solid tumor types, including triple-negative breast cancer (TNBC), respond poorly to immunotherapy due to low infiltration of CD8+ T cells into the tumor core. The extracellular matrix (ECM) and its components such as collagen have been found to contribute to immune cell exclusion. Discoidin domain receptor 1 (DDR1) is a collagen receptor known to be aberrantly expressed in TNBC among multiple solid tumor types. We have uncovered a previously unappreciated function of DDR1 in immune exclusion through shaping a collagen fiber-based tumor defense against anti-tumor immunity (Sun et al, Nature 599, 673-678 (2021)). Our study showed that deletion of DDR1 in mouse mammary carcinoma cell lines such as E0771 and M-Wnt (syngeneic with C57BL/6 strain background) promotes infiltration of CD8+ T cells and reduces tumor growth in an immunocompetent mouse model. Extending the published study to other immunocompetent mouse strain backgrounds, we observed that deletion of DDR1 in EMT6 cells, another immune excluded TNBC mouse model in the BALB/c strain, increased the infiltration of CD8+ T cells to the tumor core and reduced tumor growth. Data concerning the DDR1-dependent spatial architecture of the mammary tumor microenvironment will be presented. Identifying specific immune and stromal cell populations and proteins spatially modified in the presence or absence of DDR1 may aid in development of new stand-alone or combination anti-cancer treatments with anti DDR1 antibody. Citation Format: Payal Mitra, Jorge Azpurua, Huai-Chin Chiang, Rong Li. Understanding the role of immune exclusion in mammary tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5568.