Fig. 2.

Transcription factors specifying CAF Subtypes. Three main CAF populations have been described: inflammatory, iCAF characterized by cytokine/chemokine secretion; myofibroblasts, myCAF providing ECM modulation, collagen deposition; antigen-presenting CAF, apCAF expressing major histocompatibility complex (MHC) class II genes. TFs associated with each of the CAF subtype are reported. Additional subtypes were defined by scRNA-seq. From 3 tumor histotypes, melanoma, head and neck squamous cell carcinoma, and lung cancer, 6 different subtypes including pan-myCAF, pan-dCAF, pan-iCAF, have been identified and associated with specific transcription factors (3 Tumor types) [8]. From scRNA-seq data of 9 studies of pan-cancer CAF atlas, four different CAF subtypes, namely progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF), and matrix-producing CAF (matCAF) emerged as associated with core regulatory network of transcription factors (TFs), that are highly activated in CAF subtypes with similar functionality (9 tumor types) [92]. Finally, transcriptomic profiles of fibroblasts from multiple tumor types (10 tumor types) different clusters have been identified, with three major components, including cancer-associated myofibroblasts (CAFmyo), inflammatory CAFs (CAFinfla), and adipogenic CAFs (CAFadi), along with minor components, such as endothelial-to-mesenchymal transition CAF (CAFEndMT), peripheral nerve-like CAF (CAFPN), and antigen-presenting CAF (CAFap) [9]. Created with BioRender.com