Friend or foe: The paradoxical roles of cancer-associated fibroblasts in tumour immunotherapy

Cancer-associated fibroblasts (CAFs) represent critical cellular components of the tumor microenvironment and have garnered widespread attention in the field of tumor immunology. However, given the pronounced heterogeneity of CAFs, research investigating their impact on tumor immunity has yielded diverse and often contradictory results. Therefore, in this review, we have systematically summarized previous studies to comprehensively elucidate the role of CAFs in the tumor immune microenvironment and have explored the bidirectional regulatory effects of CAFs on immune cells and immune molecules within this complex niche. We highlight the multifaceted role of CAFs in cancer immunotherapy, focusing on their impact on immunotherapeutic efficacy, as well as the synergistic effects between CAF-targeted therapies and immunotherapies in anti-cancer treatment. Addressing the heterogeneity of CAFs, we also critically analyze controversies surrounding these cells in the field of tumor immunology and propose strategic directions for future investigations targeting this cell population. Our comprehensive analysis provides a strategic framework for future research directions and clinical translation of CAF-targeted strategies, ultimately facilitating the development of more effective and personalized cancer immunotherapeutic approaches.