Abstract 5217: Interaction of cancer associated fibroblasts and apoptotic cancer cells reduces macrophage survival and promotes reprograming of tumor associated macrophages

Recent studies highlight the critical role of cancer-associated fibroblasts (CAFs)- tumor-associated macrophages (TAMs) interactions in tumorigenesis. In prior work, we demonstrated that the interaction between CAFs and apoptotic cancer cells can inhibit tumor growth and metastasis. However, the molecular mechanisms underlying the crosstalk between CAFs reprogrammed by apoptotic cancer cells and TAMs are incompletely understood. In this study, we show, using immunohistochemistry in primary tumors, that intratumoral injection of conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells reduces the density of tumor-associated macrophages (TAMs) and the proportion of M2 TAMs. Additionally, this treatment shifts M2 TAMs toward an M1-like phenotype within the tumor microenvironment (TME). Furthermore, CM from apoptotic cancer cell-exposed CAFs promotes STAT1 phosphorylation in M2 TAMs. Depletion of WISP-1 from the CM reversed these effects, emphasizing its pivotal role. These findings suggest that CM from apoptotic cancer cell-exposed CAFs may provide a promising therapeutic strategy for targeting TAMs in the TME. Citation Format: Jihee Lee Kang, Kyungwon Yang, Kiyoon Kim. Interaction of cancer associated fibroblasts and apoptotic cancer cells reduces macrophage survival and promotes reprograming of tumor associated macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5217.