CAF subpopulations comprise three functional classes (superclusters)
1]steady state (steady state-like…SSL)
2] mechanoresponsive (mechanoresponsive ….MR)
3] immunomodulatory (immunomodulatory …IM ).
Cancer-associated fibroblasts (CAFs) are an integral part of the solid tumor microenvironment, and the balance between CAF superclusters has important translational implications.
Solid tumors contribute to more than 80% of cancer deaths. For most types of solid tumors, treatment involves a combination of chemotherapy, radiation, and surgery. Approaches that target multiple cell types in the tumor microenvironment (TME) improve therapeutic efficacy. The TME consists of transformed tumor cells along with non-transformed stromal cells including immune cells, CAFs.
Clinically, solid tumors are often recognized by their firm texture compared to benign parenchyma. This is attributed to CAFs, which secrete extracellular matrix components (e.g. collagens), creating a dense fibrous network (desmoplasia) in the tumor Despite their abundance in solid tumors, CAFs are not targeted in primary cancer therapy because the heterogeneity and the functions of CAF remain poorly understood CAFs facilitate tumor proliferation, invasion and metastasis and are often associated with poor prognosis.
However, indiscriminate downregulation of CAF may accelerate tumor progression. CAF heterogeneity is perhaps best characterized in terms of cell surface marker expression. They express normal markers associated with fibroblasts, however, there is no single marker for all CAFs. In addition, it has yet to be determined whether individual CAF subpopulations are maintained across all tumor types and species.
SOURCE: [Cancer cell Oct.2022]
