Dynamic plasticity of cancer-associated fibroblasts during tumor progression: emerging concepts

Cancer-associated fibroblasts (CAFs) are a predominant cellular component of the stroma in many solid cancers and play critical roles in cancer progression and therapeutic response. Recent single-cell transcriptomic analyses identified different subpopulations of CAFs, including myofibroblastic CAFs, inflammatory CAFs and antigen-presenting CAFs. Pseudotime analyses reveal that CAFs are highly plastic, switching in response to changing tumor-derived cues and microenvironmental signals. While many reviews have described CAF heterogeneity and functional diversity as relatively static features, emerging evidence suggests that CAF identity evolves dynamically during tumor progression. In this review, we specifically emphasize the dynamic heterogeneity and plasticity of CAFs. By integrating insights from multiple human cancer types, including breast, liver, lung and pancreatic cancers, this review highlights how cancer cells shape the CAF phenotype that sustains tumor progression in turn. Understanding the complex intercellular dialogue in the tumor microenvironment and deciphering the molecular mechanisms underlying CAF plasticity open new prospects for targeting the “right CAF subset at the right time” to improve patient prognosis.