Targeting cancer-associated fibroblasts in immunotherapy

Abstract Cancer-associated fibroblasts (CAF) are the most prevalent tumor stroma cells and greatly influence the development of cancer by regulating the tumor microenvironment (TME) in various ways. CAF provide a physical support for cancer to grow and metastasize through remodeling of TMEs, and secrete various signaling substances that promote tumor progression or metabolically provide energy sources necessary for cancer proliferation. In particular, CAF promote the ability of a tumor to escape immune surveillance by interacting with various immune cells. Therefore, understanding and targeting CAF are critical aspects of the success or failure of anti-cancer treatment. Given the limited therapeutic outcomes of chemotherapy or immunotherapy, increasing research interest has focused on the importance of CAF in anticancer immunotherapy. To date, various targeting strategies and nanomaterials have been applied for CAF targeting to potentiate the efficacy of immunotherapy. Regardless of the approach, a common concept has been the deactivation or elimination of CAF, with the goal of suppressing the immune-regulating mechanisms of CAF, remodeling the TME, and increasing immunotherapeutic effects alone or combination with existing immunotherapy. This chapter reviews the concepts and research trends of CAF targeting and suggests directions for future efforts.