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Peer-reviewedCC BY 4.0Frontiers in Immunology

Cancer-associated fibroblasts: multifaceted regulators of the tumor microenvironment and emerging therapeutic targets

  • Jinsong Yu1
  • Han Yang2
  • Xiaofang Zhu3
  1. 1Center for Plastic & Reconstructive Surgery, Department of Lymphatic Surgery and Reconstructive Microsurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College
  2. 2Department of Endocrinology, Nanyang Nanshi Hospital
  3. 3Center for General Practice Medicine, Department of Nursing, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College
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Abstract

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of nonmalignant stromal cells that influence tumor progression and treatment response. They can arise from resident fibroblasts and other progenitor populations, with their relative contributions varying across tumor types and experimental settings. CAF states and functions are shaped by their cellular origins, local signals, spatial niches, and therapeutic pressure. CAFs participate in extracellular matrix remodeling, immune regulation, metabolic interactions, and angiogenesis, with effects that can promote or restrain tumor progression depending on tumor type and local conditions. This review summarizes CAF origins, molecular states, functional diversity, and signaling networks. We assess therapeutic strategies involving CAF depletion, extracellular matrix modification, signaling disruption, and phenotypic normalization, distinguishing preclinical findings from clinical outcomes. The clinical benefit of these approaches requires further validation in defined patient populations. Finally, we discuss how single-cell and spatial profiling and patient-derived models may improve CAF characterization and inform the development of selective stromal interventions.

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Cite

BibTeXRIS
BibTeX
@article{yu2026cancerassociated,
  title = {{Cancer-associated fibroblasts: multifaceted regulators of the tumor microenvironment and emerging therapeutic targets}},
  author = {Jinsong Yu and Han Yang and Xiaofang Zhu},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1990436},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990436/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cancer-associated fibroblasts: multifaceted regulators of the tumor microenvironment and emerging therapeutic targets
AU  - Jinsong Yu
AU  - Han Yang
AU  - Xiaofang Zhu
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1990436
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990436/full
AB  - Cancer-associated fibroblasts (CAFs) are a heterogeneous population of nonmalignant stromal cells that influence tumor progression and treatment response. They can arise from resident fibroblasts and other progenitor populations, with their relative contributions varying across tumor types and experimental settings. CAF states and functions are shaped by their cellular origins, local signals, spatial niches, and therapeutic pressure. CAFs participate in extracellular matrix remodeling, immune regulation, metabolic interactions, and angiogenesis, with effects that can promote or restrain tumor progression depending on tumor type and local conditions. This review summarizes CAF origins, molecular states, functional diversity, and signaling networks. We assess therapeutic strategies involving CAF depletion, extracellular matrix modification, signaling disruption, and phenotypic normalization, distinguishing preclinical findings from clinical outcomes. The clinical benefit of these approaches requires further validation in defined patient populations. Finally, we discuss how single-cell and spatial profiling and patient-derived models may improve CAF characterization and inform the development of selective stromal interventions.
SN  - 1664-3224
ER  -