Cancer-associated fibroblasts and innate immune cells: orchestrators of the immunosuppressive tumor microenvironment
9 affiliations
- 1Department of Pathology, Gomel State Medical University
- 2Department of Prevention and Treatment of Wound Infections, National Medical Research Center of Traumatology and Orthopedics named after R.R. Vreden
- 3Department of Pathologycal Anatomy, North-Western State Medical University named after I.I. Mechnikov
- 4Department of Chemical Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia
- 5Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza
- 6Department of Radiology and Radiotherapy, Gomel State Medical University
- 7National Molecular Genetics Laboratory of Cancer Research, N.N. Alexandrov National Cancer Center of Belarus
- 8Department of Obstetrics and Gynecology, Gomel State Medical University
- 9School of Life Sciences, University of Sussex
Abstract
The tumor microenvironment (TME) represents a complex, dynamic, and heterogeneous system in which stromal and immune elements interact to influence tumor development and mechanisms of immune escape. Within the stromal compartment, cancer-associated fibroblasts (CAFs) have been identified as key mediators of immune regulation in the TME. Emerging evidence indicates that CAFs engage in extensive crosstalk with innate immune cell populations—including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), natural killer (NK) cells, mast cells, and dendritic cells (DCs). Through these interactions, CAFs contribute to the establishment and maintenance of an immunosuppressive milieu that supports tumor progression and facilitates immune evasion. This review summarizes the molecular interactions between CAFs and innate immune cells in the TME. It highlights how CAF-derived factors such as IL-6, TGF-β, CXCL12, and CSF-1 regulate immune cell recruitment and polarization, promoting immunosuppression, tumor progression, angiogenesis, and metastasis. Additionally, feedback signals from immune cells further sustain CAF activation, creating a self-reinforcing immunosuppressive microenvironment. Elucidating these multidirectional interactions offers important insights into tumor biology and identifies promising therapeutic avenues. Targeting CAF-associated signaling pathways or interfering with CAF–immune cell communication may help restore anti-tumor immune responses and improve the effectiveness of cancer immunotherapy strategies.
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BibTeX
@article{zinovkin2026cancerassociated,
title = {{Cancer-associated fibroblasts and innate immune cells: orchestrators of the immunosuppressive tumor microenvironment}},
author = {Dmitry A. Zinovkin and Yulia S. Korneva and Heba Mohammed Arafat and Ohood Mohammed Shamallakh and Ekaterina S. Zinovkina and Denis A. Davydov and Anna S. Portyanko and Irina I. Slepokurova and Yulia A. Lyzikova and Md Zahidul Islam Pranjol},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1876751},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1876751/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cancer-associated fibroblasts and innate immune cells: orchestrators of the immunosuppressive tumor microenvironment
AU - Dmitry A. Zinovkin
AU - Yulia S. Korneva
AU - Heba Mohammed Arafat
AU - Ohood Mohammed Shamallakh
AU - Ekaterina S. Zinovkina
AU - Denis A. Davydov
AU - Anna S. Portyanko
AU - Irina I. Slepokurova
AU - Yulia A. Lyzikova
AU - Md Zahidul Islam Pranjol
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1876751
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1876751/full
AB - The tumor microenvironment (TME) represents a complex, dynamic, and heterogeneous system in which stromal and immune elements interact to influence tumor development and mechanisms of immune escape. Within the stromal compartment, cancer-associated fibroblasts (CAFs) have been identified as key mediators of immune regulation in the TME. Emerging evidence indicates that CAFs engage in extensive crosstalk with innate immune cell populations—including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), natural killer (NK) cells, mast cells, and dendritic cells (DCs). Through these interactions, CAFs contribute to the establishment and maintenance of an immunosuppressive milieu that supports tumor progression and facilitates immune evasion. This review summarizes the molecular interactions between CAFs and innate immune cells in the TME. It highlights how CAF-derived factors such as IL-6, TGF-β, CXCL12, and CSF-1 regulate immune cell recruitment and polarization, promoting immunosuppression, tumor progression, angiogenesis, and metastasis. Additionally, feedback signals from immune cells further sustain CAF activation, creating a self-reinforcing immunosuppressive microenvironment. Elucidating these multidirectional interactions offers important insights into tumor biology and identifies promising therapeutic avenues. Targeting CAF-associated signaling pathways or interfering with CAF–immune cell communication may help restore anti-tumor immune responses and improve the effectiveness of cancer immunotherapy strategies.
SN - 1664-3224
ER -