Abstract 4640: CAF contributes to cancer progression through its immunomodulatory role within the tumor microenvironment

Abstract

Introduction: Cancer progression and metastatic spread is modulated by the tumor microenvironment. Cancer-associated fibroblasts (CAF) are the most abundant cell type within the tumor microenvironment. Little is known about the specific mechanisms by which CAF would exert its cancer progression, through the high secretory capacity of soluble pro-tumorigenic molecules and remodeling of the extracellular matrix. Recent studies in our laboratory have shown for the first time that CAF derived from patients without metastasis express a different genetic profile than those with metastases (mCAF). This study seeks to evaluate the contribution of mCAF to tumor progression through its immunomodulatory role. Methodology: mCAFs were obtained from patients with metastatic disease and BAF from benign patients. The fibroblasts were functionally characterized by the generation of fibroblast-derived matrices (FDM) and secretory profiles by cytokine array. CD8 T lymphocytes were obtained from healthy patients and treated with fibroblast-secretome. Markers were studied by flow cytometry: activation (CD25 and CD69) and repression (LAG3 and PD1). The migration of CD8 T lymphocytes was studied by transwell and agarose drop migration assay. Results and conclusion: FDM of mCAF are different in their composition and organization. Furthermore, the secretome of each type of fibroblast presents a differential effect on the activation of CD8 T cells according to the markers highlighted. Regarding migration, it has been observed that the mCAF-secretome can attract lymphocytes. However, it would lead them to apoptosis. Our results suggest that mCAF, within the tumor microenvironment, has an immunomodulatory role on CD8 T lymphocytes. Acknowledgment: Beca Doctorado Nacional ANID 21181427 Citation Format: Muriel Antonieta Núñez, Oreste Corrales, Victoria Velasquez, Daniel Ernst, Montecinos Viviana, Francisco Nualart, María Isabel Yuseff, Javier Cerda-Infante. CAF contributes to cancer progression through its immunomodulatory role within the tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4640.