Fig. 1. Cancer-associated fibroblasts (CAFs) are a heterogeneous and plastic population within the tumor microenvironment.

The heterogeneity of fibroblasts could be attributed to the multiple origins of the precursor cells, the phenotypical diversity of subsets and the distinct function of each subset. Potential cellular sources include local tissue resident stellate cells and normal fibroblasts and nonfibroblast lineage or recruited bone marrow-derived mesenchymal stem cells (MSCs) and macrophages. The main subsets of CAFs include myCAFs, iCAFs and apCAFs, which exhibit different biological features and result in phenotypical diversity and functional heterogeneity in cancer progression. However, the distinct subsets of CAFs are not permanent but interconvertible via manipulation of specific signaling, as shown by the conversion between iCAFs and myCAFs via the TGFβ or IL-6 signaling pathway of CAFs. myCAFs: myofibroblast-like CAFs; iCAFs: inflammatory CAFs; apCAFs: antigen-presenting CAFs.