Chapter 3 - Role of cancer-associated fibroblasts in tumor microenvironment

Abstract

The tumor microenvironment has been identified as a target-rich setting for the production of new antitumor drugs throughout the last decade. Cancer-associated fibroblast (CAFs), possessing a spindle shape that contributes to and alters the ECM structure, are prominent constituents of the TME. CAFs possess functional and phenotypic diversity and are significant constituents of the tumor microenvironment. Besides altering the ECM, the activation of CAFs plays a significant part in tumor growth, migration, and metastasis via various mechanisms. Various studies have already demonstrated the importance of tumor cell and CAF interaction during tumor growth and development. However, the combined interaction of CAFs and the tumor immune microenvironment (TIME) has recently been greatly identified as another critical element in tumor growth. The TIME is primarily composed of various immune cell types residing with the tumor and is strongly connected with the TME's antitumor immunological state. There occurs the interaction between various immune components and the CAFs through the secretion of various substances that lead to immune surveillance evasion. In-depth investigations of CAFs and their interactions with the TIME may yield innovative techniques for later targeted immunotherapies. We discuss recent developments in understanding the direct and indirect interplay between CAFs and TIME and highlight the probable immunosuppressive pathways caused by CAFs in the TME. Additionally, we discuss existing CAF-targeting immunotherapies and shed light on possible future directions for CAF research at the conclusion.