Journal Article Review Epublish
PubMed: 40805183 DOI: 10.3390/cancers17152484
Cancer-Associated Fibroblasts: Immunosuppressive Crosstalk with Tumor-Infiltrating Immune Cells and Implications for Therapeutic Resistance.
Cancers (Basel) 17(15)
Authors: Jogendra Singh Pawar, Md Abdus Salam, Md Shalman Uddin Dipto, Md Yusuf Al-Amin, Moushumi Tabassoom Salam, Sagnik Sengupta, Smita Kumari, Lohitha Gujjari, Ganesh Yadagiri
Affiliations
- Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
- The James Cancer Hospital and Solove Research Institute, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
- Faculty of Biotechnology & Biomedical Engineering, Rajshahi Medical University, Rajshahi 6100, Bangladesh.
- Department of Pharmacy, University of Rajshahi, Rajshahi 6205, Bangladesh.
- Purdue University Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN 47907, USA.
- Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Dorothy M. Davis Heart and Lung Research Institute, Division of Pulmonary, Critical Care & Sleep Medicine, Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
- Department of Obstetrics and Gynecology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Abstract
Cancer is no longer considered as an isolated event. Rather, it occurs because of a complex biological drive orchestrating different cell types, growth factors, cytokines, and signaling pathways within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most populous stromal cells within the complex ecosystem of TME, with significant heterogeneity and plasticity in origin and functional phenotypes. Very enigmatic cells, CAFs determine the progress and outcomes of tumors through extensive reciprocal signaling with different tumors infiltrating immune cells in the TME. In their biological drive, CAFs release numerous chemical mediators and utilize various signaling pathways to recruit and modulate tumor-infiltrating immune cells. The CAF-induced secretome and exosomes render immune cells ineffective for their antitumor activities. Moreover, by upregulating immune inhibitory checkpoints, CAFs create an immunosuppressive TME that impedes the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TILs). Further, by depositing and remodeling extracellular matrix (ECM), CAFs reshape the TME, which enhances tumor growth, invasion, metastasis, and chemoresistance. Understanding of CAF biology and its crosstalk with tumor-infiltrating immune cells is crucial not only to gain insight in tumorigenesis but to optimize the potential of novel targeted immunotherapies for cancers. The complex relationships between CAFs and tumor-infiltrating immune cells remain unclear and need further study. Herein, in this narrative review we have focused on updates of CAF biology and its interactions with tumor-infiltrating immune cells in generating immunosuppressive TME and resistance to cell death.
MeSH
Cells, Growth, Neoplasms, Cancer-Associated Fibroblasts, Fibroblasts, Therapeutics, Tumor Microenvironment