Journal
SEMINARS IN IMMUNOLOGY
Volume 48, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2020.101417
Keywords
Cancer associated fibroblasts; CAF; Immunosuppression; Cancer; Tumor microenvironment; Stroma; T lymphocytes; NK; Macrophages
Categories
Funding
- Institut National du Cancer (INCa)
- Simone and Cino del Duca Foundation
- Ligue Nationale Contre le Cancer (Labelisation)
- Inserm [PC201317]
- Institut Curie (Incentive and Cooperative Program Tumor Micro-environment PIC TME/T-MEGA, PIC3i CAFi)
- ICGex [ANR-10-EQPX-03]
- SIRIC [INCa-DGOS-4654]
- INCa [INCa-DGOS-9963, INCa-11692, INCa-DGOS-Inserm12554]
- Foundation Chercher et Trouver
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In tumors, Cancer-Associated Fibroblasts (CAFs) constitute the most prominent component of the tumor microenvironment (TME). CAFs are heterogeneous and composed of different CAF subsets exerting distinct functions in tumors. Specific CAF subpopulations actively influence various aspects of tumor growth, including cancer cell survival and proliferation, angiogenesis, extracellular matrix (ECM) remodeling, metastatic spread and chemoresistance. During the past decade, some CAF subsets have also been shown to modulate anti-tumor immune response. Indeed, they can increase the content in regulatory T lymphocytes and inhibit the activity of effector and cytotoxic immune cells. These functions are mainly controlled by their constitutive secretion of cytokines, chemokines, growth factors and ECM proteins, either directly in the surrounding extracellular space or through micro-vesicles. Some CAFs also express key regulators of immune checkpoints. The different roles played by CAFs, both as immunosuppressor or as physical support for tumor cell progression, set them as promising targets for anti-tumor therapies. In this review, we describe the main current knowledge on CAFs heterogeneity and immunosuppressive microenvironment, as well as their potential therapeutic implications.
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