Fibroblast heterogeneity in tumor micro-environment: Role in immunosuppression and new therapies
•CAFs exhibit a phenotypic heterogeneity that define their functions in tumors.•Different CAF subsets are associated with an immunosuppressive microenvironment.•CAFs immunosuppressive functions act on both innate and adaptive immune response.•CAFs emerge as an attractive target for the development o...
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description | •CAFs exhibit a phenotypic heterogeneity that define their functions in tumors.•Different CAF subsets are associated with an immunosuppressive microenvironment.•CAFs immunosuppressive functions act on both innate and adaptive immune response.•CAFs emerge as an attractive target for the development of anti-cancer therapies.
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. |
doi_str_mv | 10.1016/j.smim.2020.101417 |
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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.</description><identifier>ISSN: 1044-5323</identifier><identifier>EISSN: 1096-3618</identifier><identifier>DOI: 10.1016/j.smim.2020.101417</identifier><identifier>PMID: 33077325</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>CAF ; Cancer ; Cancer associated fibroblasts ; Immunosuppression ; Life Sciences ; Macrophages ; Stroma ; T lymphocytes ; Tumor microenvironment</subject><ispartof>Seminars in immunology, 2020-04, Vol.48, p.101417-101417, Article 101417</ispartof><rights>2020 The Author(s)</rights><rights>Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><rights>Attribution - NonCommercial</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-38c10c9098158117c32fc87186bd7b2f502358bbccfe230c677e1cf081e852553</citedby><cites>FETCH-LOGICAL-c434t-38c10c9098158117c32fc87186bd7b2f502358bbccfe230c677e1cf081e852553</cites><orcidid>0000-0002-3751-6989</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.smim.2020.101417$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33077325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03493637$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Mhaidly, Rana</creatorcontrib><creatorcontrib>Mechta-Grigoriou, Fatima</creatorcontrib><title>Fibroblast heterogeneity in tumor micro-environment: Role in immunosuppression and new therapies</title><title>Seminars in immunology</title><addtitle>Semin Immunol</addtitle><description>•CAFs exhibit a phenotypic heterogeneity that define their functions in tumors.•Different CAF subsets are associated with an immunosuppressive microenvironment.•CAFs immunosuppressive functions act on both innate and adaptive immune response.•CAFs emerge as an attractive target for the development of anti-cancer therapies.
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.</description><subject>CAF</subject><subject>Cancer</subject><subject>Cancer associated fibroblasts</subject><subject>Immunosuppression</subject><subject>Life Sciences</subject><subject>Macrophages</subject><subject>Stroma</subject><subject>T lymphocytes</subject><subject>Tumor microenvironment</subject><issn>1044-5323</issn><issn>1096-3618</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kcFO3DAQhq2qVaG0L8AB5dgesvXYSewgLggVqLRSpQrObuJMWK9iO9jOIt6-SQMce_Jo9M0n-f8JOQW6AQrV9_0mWmM3jLJ_iwLEO3IMtK5yXoF8v8xFkZec8SPyKcY9pZQXEj6SI86pEJyVx-TPtWmDb4cmpmyHCYN_QIcmPWfGZWmyPmTW6OBzdAcTvLPo0nn22w-4AMbayfk4jWPAGI13WeO6zOFTlnYYmtFg_Ew-9M0Q8cvLe0Lur3_cXd3m2183P68ut7kueJFyLjVQXdNaQikBhOas11KArNpOtKwvKeOlbFute2Sc6koIBN1TCShLVpb8hHxbvbtmUGMwtgnPyjdG3V5u1bKb_17ziosDzOzXlR2Df5wwJmVN1DgMjUM_RcWKWUmB1fWMshWdM4gxYP_mBqqWFtReLS2opQW1tjAfnb34p9Zi93byGvsMXKwAzokcDAYVtUGnsTMBdVKdN__z_wU69Jhl</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Mhaidly, Rana</creator><creator>Mechta-Grigoriou, Fatima</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-3751-6989</orcidid></search><sort><creationdate>20200401</creationdate><title>Fibroblast heterogeneity in tumor micro-environment: Role in immunosuppression and new therapies</title><author>Mhaidly, Rana ; Mechta-Grigoriou, Fatima</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-38c10c9098158117c32fc87186bd7b2f502358bbccfe230c677e1cf081e852553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>CAF</topic><topic>Cancer</topic><topic>Cancer associated fibroblasts</topic><topic>Immunosuppression</topic><topic>Life Sciences</topic><topic>Macrophages</topic><topic>Stroma</topic><topic>T lymphocytes</topic><topic>Tumor microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mhaidly, Rana</creatorcontrib><creatorcontrib>Mechta-Grigoriou, Fatima</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Seminars in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mhaidly, Rana</au><au>Mechta-Grigoriou, Fatima</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fibroblast heterogeneity in tumor micro-environment: Role in immunosuppression and new therapies</atitle><jtitle>Seminars in immunology</jtitle><addtitle>Semin Immunol</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>48</volume><spage>101417</spage><epage>101417</epage><pages>101417-101417</pages><artnum>101417</artnum><issn>1044-5323</issn><eissn>1096-3618</eissn><abstract>•CAFs exhibit a phenotypic heterogeneity that define their functions in tumors.•Different CAF subsets are associated with an immunosuppressive microenvironment.•CAFs immunosuppressive functions act on both innate and adaptive immune response.•CAFs emerge as an attractive target for the development of anti-cancer therapies.
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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33077325</pmid><doi>10.1016/j.smim.2020.101417</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3751-6989</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | CAF Cancer Cancer associated fibroblasts Immunosuppression Life Sciences Macrophages Stroma T lymphocytes Tumor microenvironment |
title | Fibroblast heterogeneity in tumor micro-environment: Role in immunosuppression and new therapies |
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