# The Significance of the Heterogeneity of Cancer-Associated Fibroblasts in Tumor Microenvironments

## TL;DR

This review discusses how different types of cancer-associated fibroblasts contribute to tumor progression and cancer treatment challenges.

## Contribution

The paper highlights the importance of CAF heterogeneity and its role in tumor development and response to therapy.

## Key findings

- CAFs include subtypes like apCAFs, myCAFs, and iCAFs, each with distinct roles in tumor progression.
- Cell interactions among CAF subtypes may influence the development of various carcinomas.
- Understanding CAF heterogeneity could improve precision cancer treatments.

## Abstract

The tumor heterogeneity that is frequently observed in cancer tissues comprises not only cancer cells but also stromal cells in the tumor microenvironment. One of the major components of tumor stroma, i.e., cancer-associated fibroblasts (CAFs), play crucial roles in tumor progression and the tumor response to chemotherapy. The known subtypes of CAFs are antigen-presenting CAFs (apCAFs), myofibroblastic CAFs (myCAFs), and inflammatory CAFs (iCAFs). It has been speculated that (i) the heterogeneity of CAF subtypes might contribute to tumor progression; (ii) cell-to-cell interactions among CAF subtypes in tumors might be associated with the development of various types of carcinomas, and (iii) juxtracrine and/or paracrine signaling from CAFs may play important roles in this development. A clarification of the mechanisms that underlie the tumoral heterogeneity of CAFs could contribute to cancer treatment as precision medicine. This review explains the significance of CAF heterogeneity in tumor microenvironments, especially concerning the CAF subtypes.