Regulation of cancer-associated fibroblasts for enhanced cancer immunotherapy using advanced functional nanomedicines: an updated review

Abstract

The tumor microenvironment (TME) is a complex and dynamic ecosystem that plays a critical role in cancer progression. It comprises various cell types, including immune cells, tumor cells, and stromal cells. Among these, cancer-associated fibroblasts (CAFs) represent a heterogeneous population with diverse origins, phenotypes, and functions. Activated CAFs secrete multiple factors that promote tumor growth, migration, angiogenesis, and contribute to chemoresistance. Additionally, CAFs secrete extracellular matrix (ECM) components, such as collagen, which form a physical barrier that hinders the penetration of chemotherapeutic and immunotherapeutic agents. This ECM also influences immune cell infiltration, impeding their ability to effectively target tumor cells. As a result, modulating the activity of CAFs has emerged as a promising strategy to enhance the efficacy of tumor immunotherapy. Nano-delivery systems, constructed from various nanomaterials with high targeting specificity and biocompatibility, offer a compelling approach to deliver therapeutic agents or immunomodulatory factors directly to CAFs. This modulation can alter CAF function, reduce their tumor-promoting effects, and thereby improve the outcomes of immunotherapy. This review provides an in-depth exploration of the origins, functions, and interactions of CAFs within the TME, particularly in the context of immune suppression. Furthermore, it discusses the potential applications of functional nanocarrifers in modulating CAFs and enhancing the effectiveness of tumor immunotherapy, highlighting the significant progress and potential of nanotechnology in this area.