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Cancer-associated fibroblasts (CAFs): a new challenge for pathologists and oncologists, and a promising target for a modern oncotherapy

ABSTRACT
According to the “seed and soil” theory, cancer progression is influenced by the crosstalk between tumor cells and the surrounding tumor microenvironment (TME). TME comprises several cell types, including tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), lymphocytes, leukocytes, vascular endothelial cells, pericytes, and fibroblasts.
Cancer-associated fibroblasts (CAFs) are a crucial component of the TME and contribute to tumor development and progression. CAFs are a heterogeneous population originating from different cells including resident fibroblasts, circulating fibrocytes, smooth muscle vascular cells, endothelial cells, mesothelial cells, and organ-specific cells such as hepatic stellate cells in the liver.
CAFs can play a dual role in the development and progression of tumors, acting as both promoters and inhibitors of tumor growth. The acquisition of a hypermethylated state is associated with a protumorigenic phenotype. Multiple subtypes have been identified in CAFs: inflammatory (iCAFs), myofibroblastic (myCAFs), antigen-presenting (apCAFs), complement-secreting (csCAFs), and CAFs with high metabolic state (meCAFs). In this review, we will discuss the origin of CAFs, their heterogeneity, their interaction with the other components of the TME, and their role in cancer insurgence and progression. The immunohistochemical marker useful for the identification of CAF subtypes in clinical practice will be discussed.
The mechanisms by which CAFs may promote cancer angiogenesis, inhibit cancer cell apoptosis, and induce epithelial-to-mesenchymal transition will be analyzed.
In the final part, targeted therapies for CAFs, including their direct removal, the inhibition of CAF signaling, and CAF reprogramming will be discussed.

IMPACT STATEMENT
Our work highlights the role that components of the tumor microenvironment play in tumor growth and progression. In particular, tumor-associated fibroblasts, which could be useful therapeutic targets in the future.

 

Table of Content: Vol. 4 (No. 2) 2024 June

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