alexa Cancer-associated Fibroblasts and Modulation of the Antitumor Immune Response | Open Access Journals
ISSN: 1747-0862
Journal of Molecular and Genetic Medicine
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Cancer-associated Fibroblasts and Modulation of the Antitumor Immune Response

Linda Ziani1,2,3, Salem Chouaib1,2,3* and Jerome Thiery1,2,3

1INSERM, U1186, Villejuif, France

2Gustave Roussy Cancer Campus, Villejuif, France

3University Paris-Saclay, Faculty of Medicine, Le Kremlin Bicêtre, France

Corresponding Author:
Salem Chouaib
Gustave Roussy Cancer Campus
Villejuif, France
Tel: 33142114211
E-mail: [email protected]

Received date: December 12, 2015 Accepted date: December 20, 2015 Published date: December 27, 2015

Citation:Ziani L, Chouaib S, Thiery J (2015) Cancer-associated Fibroblasts and Modulation of the Antitumor Immune Response. J Mol Genet Med 9:193. doi:10.4172/1747-0862.1000193

Copyright: © 2015 Ziani L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Visit for more related articles at Journal of Molecular and Genetic Medicine

Description

During tumor progression, tumor cells proliferate under adverse host conditions and use several survival strategies to block the action of key regulators of the immune response and circumvent anti-tumor defenses. Consequently, the current development of new immunotherapeutic strategies aimed at inducing or optimizing the immune response directed against the tumor and opened the way to new treatments of cancers. Besides the several known classical strategies used by tumor cells to escape to immune surveillance, it should be noted that the evasion of immunosurveillance by tumor cells is also under the control of the tumor microenvironment complexity and plasticity [1,2].

Introduction

Among the stromal cells, activated fibroblasts, termed cancerassociated fibroblasts (CAFs), play a critical role in the complex process of tumor-stroma interaction. CAFs, one of the prominent stromal cell population in most types of human carcinomas, are α- SMA (alpha-smooth muscle actin) positive, spindle-shaped cells, who closely resemble normal myofibroblasts but express specific markers (ie, FAP (fibroblast-associated protein), PDGFR-β (platelet-derived growth factor)) together with the fibroblastic marker FSP-1 (fibroblast specific protein 1) and vimentin (a mesenchymal marker). CAFs are also characterized by the absence of epithelial (cytokeratin, Ecadherin), endothelial (CD31) and fully differentiated smooth muscle (smoothelin) markers [3]. CAFs differentiate and proliferate in the tumor microenvironment in a transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF)-dependent manner from other cell types such as resident fibroblasts, mesenchymal stem cells, endothelial and epithelial cells [4,5]. In the tumor stroma, CAFs interact with tumor cells and secrete several factors such as extracellular matrix proteins (ie, collagen), matrix metallo-proteinases (MMPs), proteoglycans (ie, laminin, fibronectin), chemokines (ie, CXCL1, CXCL2, CXCL8, CXCL6, CXCL12/SDF1, CCL2 and CCL5), vascularisation promoting factors (ie, PDGF and VEGF) and other proteins which affect tumor cells proliferation, invasiveness, survival and stemness (ie, TGF-β, EGF, HGF, FGF, PGE2) [5]. Consequently, CAFs have been involved in tumor growth, angiogenesis, cancer stemness, extracellular matrix (ECM) remodelling, tissue invasion, metastasis and even chemoresistance [6,7].

During the past few years, these activated tumor-associated fibroblasts have also been involved in the modulation of the antitumor immune response by the secretion of immunosuppressive and pro-inflammatory factors (ie, TGF-β, IL-1β, IL6, IL10…), chemokines (ie, CXCL12, CCL2…) and chemical mediators (ie, PGE2…) in the tumor microenvironment. As such, CAFs can potentially affect both innate and adaptive antitumor immune response [8,9]. For example, the secretion of CXCL12/SDF1 and CCL2/MCP-1 by CAFs is potentially involved in macrophages attraction in the tumor microenvironment and in their differentiation into a M2 immunosuppressive phenotype [10]. CAF secretion of chemokines can also recruit immunosuppressive myeloid-derived suppressive cells (MDSC) population to the tumor [11]. The secretion of TGF-β by CAFs potentially affects dendritic cells biology by inhibiting their migration, maturation and antigen presentation capabilities, increases the numbers of regulatory T cells (Tregs) within the tumor microenvironment through the induction of FOXP3 expression [12] and interferes with cytotoxic T lymphocytes (CTL) function and frequency within the tumor [13]. The secretion of TGF-β by CAFs can also attenuate IFN-γ production by natural killer (NK) cells [14], as well as the expression of NK-activating receptors including NKG2D, NKp30 and NKp44 [12]. Similarly, the secretion of vascular endothelial growth factor (VEGF) by CAFs may affect dendritic function and increase the infiltration of Tregs and MDSC within the tumor [15]. Moreover, the secretion of prostaglandin E2 (PGE2) can decrease the expression of the activator receptor NKG2D on NK cells surface (which is also the case for indoleamine-2,3-dioxygenase (IDO) secretion by CAFs) [16] and induces FOXP3 expression in Tregs [17]. Nevertheless, further studies are clearly needed to fully elucidate the complex role of CAFs in the complex tumor immunosuppressive network.

Altogether, these findings highlight the action of CAFs on various levels of the antitumor immune response within the tumor microenvironment. Thus, combination therapy co-targeting CAFs and tumor cells or other immune check points (ie, PDL1, CTLA4) should represent a significant benefit in terms of tumor immunotherapy.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • 3rd Antibodies and Bio Therapeutics Congress & B2B
    November 08-09, 2017 Las Vegas, Nevada, USA
  • 19th World Congress on Biotechnology
    November 13-14, 2017 Osaka, Japan
  • 4th World Conference on Synthetic Biology and Genetic Engineering
    November 9-10, 2017 Singapore City, Singapore

Article Usage

  • Total views: 8477
  • [From(publication date):
    December-2015 - Oct 20, 2017]
  • Breakdown by view type
  • HTML page views : 8269
  • PDF downloads :208
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords