Abstract 950: Role of epithelial-mesenchymal plasticity in immune remodeling during metastasis

Abstract

Abstract Introduction: Breast cancer is the most prevalent type of cancer in women, accounting for 12% of all annual cancer cases worldwide with most deaths attributed to metastasis. It displays both inter- and intra-tumoral heterogeneity which is linked to epithelial-mesenchymal transition (EMT). This program involves the acquisition of a mesenchymal-like phenotype allowing cells to disseminate from the primary tumor and metastasize. However, recent studies show that tumor cells do not need to undergo complete EMT to gain invasive potential; instead, co-expression of both epithelial and mesenchymal markers is critical for metastasis. Such tumor cells are thought to display epithelial-mesenchymal plasticity (EMP) which bestows them with enhanced fitness and flexibility to fulfill diverse requirements of the metastatic cascade. Additionally, hybrid EM phenotype has been linked to immunesuppression but has been understudied due to lack to suitable models with intact immune system. Thus, this necessitates the mechanistic dissection of tumor immune microenvironment (TIME) in models with EM plasticity. To characterize the contribution of EMP to metastasis, we utilized syngeneic mouse mammary tumor cell lines, which are hybrid EM and investigated their proteomic and cytokine profile and identified several novel cytokines. Methods: Reverse Phase Protein Array (RPPA) was performed to determine the proteomic profile of tumors with EM plasticity. In addition, Luminex assay was performed to assess the cytokine/chemokine profile in above tumor models. Results: The RPPA involved a panel of 450 antibodies and showed that tumors with EM plasticity were enriched in specific immunesuppressive proteins. At the same time, Luminex analysis was suggestive of recruitment of tumor-associated macrophages (TAMs) in models with EM plasticity. Additionally, cells with EM plasticity showed the ability to induce tumor-promoting/M2-like macrophages (in vitro). Conclusions: Our data indicates that cells/tumors with EM plasticity show differential protein expression than E and M counterparts and are enriched in specific immunesuppressive proteins. Moreover, such cells have immune networks (cytokines/chemokines) that promote recruitment of TAMs - the largest myeloid infiltrate in the microenvironment of solid tumors. Thus, our study invites more attention to investigate the mechanisms of immunesuppression and metastasis in tumors with EM plasticity. Citation Format: Tanvi H. Visal. Role of epithelial-mesenchymal plasticity in immune remodeling during metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 950.