Fig. 4

Immunotherapies that target CAFs. Four general approaches that target cancer-associated fibroblasts (CAFs) for cancer immunotherapy. ① Fibroblast activation protein⁺ (FAP⁺) CAFs can be directly eliminated by transgenic technologies, immunotherapies, and oncolytic adenovirus. ② Targeting the important signals and effectors of CAFs, such as CX-chemokine ligand 12-CX chemokine receptor 4 (CXCL12-CXCR4) interaction, Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway, transforming growth factor-β (TGF-β), and Hedgehog signaling pathway, can be used to inhibit the function of CAFs. ③ A reprogramming strategy such as vitamin A and vitamin D can be adopted to dedifferentiate activated CAFs to resident (normalized) fibroblasts. ④ CAF-derived extracellular matrix (ECM) proteins and associated signaling pathway can be targeted to induce stromal depletion. CAR chimeric antigen receptor, mAb monoclonal antibody, MDSC myeloid-derived suppressor cell, TAM tumor-associated macrophage, Treg cell regulatory T cell