Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma
Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of...
Gespeichert in:
| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2011-08, Vol.71 (16), p.5412-5422 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5422 |
|---|---|
| container_issue | 16 |
| container_start_page | 5412 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 71 |
| creator | PLATONOVA, Sophia CHERFILS-VICINI, Julien FRIDMAN, Wolf-Herman SAUTES-FRIDMAN, Catherine CREMER, Isabelle DAMOTTE, Diane CROZET, Lucile VIEILLARD, Vincent VALIDIRE, Pierre ANDRE, Pascale DIEU-NOSJEAN, Marie-Caroline ALIFANO, Marco REGNARD, Jean-François |
| description | Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression. |
| doi_str_mv | 10.1158/0008-5472.can-10-4179 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_907181327</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>907181327</sourcerecordid><originalsourceid>FETCH-LOGICAL-c587t-b495270b7f00abfcb76876611c61190637ab7e91f6e613d1e089dc635892a1d33</originalsourceid><addsrcrecordid>eNqFkUFv1DAQhS0EotuFnwDyBXFK8cR2xjmuopZWrEoPcI4mjgNBib3YyaH_HkddypGDZc3oe37jN4y9A3EFoM0nIYQptMLyypIvQBQKsH7BdqClKVAp_ZLtnpkLdpnSr1xqEPo1uygBhak17hg9xDCE1fe8CSH2o6fF9fwwLS7SMgafeBj4nV9ytc4h0sTvv_DGTRN_-Ol8WB5PjlNW36zebjwfPT-u_gdvKNrRh5nesFcDTcm9Pd979v3m-ltzWxy_fr5rDsfCaoNL0alalyg6HISgbrAdVgarCsDmU4tKInXoahgqV4HsweUP9LaS2tQlQS_lnn18evcUw-_VpaWdx2TzpORdWFNbCwQDssT_ksZIo1Bmmz3TT6SNIaXohvYUx5niYwui3dbQbhG3W8Rtc7jfutsasu792WHtZtc_q_7mnoEPZ4CSpWmI5O2Y_nFKKYmA8g_Q6Y-v</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>883847361</pqid></control><display><type>article</type><title>Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>PLATONOVA, Sophia ; CHERFILS-VICINI, Julien ; FRIDMAN, Wolf-Herman ; SAUTES-FRIDMAN, Catherine ; CREMER, Isabelle ; DAMOTTE, Diane ; CROZET, Lucile ; VIEILLARD, Vincent ; VALIDIRE, Pierre ; ANDRE, Pascale ; DIEU-NOSJEAN, Marie-Caroline ; ALIFANO, Marco ; REGNARD, Jean-François</creator><creatorcontrib>PLATONOVA, Sophia ; CHERFILS-VICINI, Julien ; FRIDMAN, Wolf-Herman ; SAUTES-FRIDMAN, Catherine ; CREMER, Isabelle ; DAMOTTE, Diane ; CROZET, Lucile ; VIEILLARD, Vincent ; VALIDIRE, Pierre ; ANDRE, Pascale ; DIEU-NOSJEAN, Marie-Caroline ; ALIFANO, Marco ; REGNARD, Jean-François</creatorcontrib><description>Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-10-4179</identifier><identifier>PMID: 21708957</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Biological and medical sciences ; Carcinoma, Non-Small-Cell Lung - immunology ; Coculture Techniques ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Immunophenotyping ; K562 Cells ; Killer Cells, Natural - immunology ; Lung Neoplasms - immunology ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Pneumology ; Tumors ; Tumors of the respiratory system and mediastinum</subject><ispartof>Cancer research (Chicago, Ill.), 2011-08, Vol.71 (16), p.5412-5422</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-b495270b7f00abfcb76876611c61190637ab7e91f6e613d1e089dc635892a1d33</citedby><cites>FETCH-LOGICAL-c587t-b495270b7f00abfcb76876611c61190637ab7e91f6e613d1e089dc635892a1d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24443717$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21708957$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PLATONOVA, Sophia</creatorcontrib><creatorcontrib>CHERFILS-VICINI, Julien</creatorcontrib><creatorcontrib>FRIDMAN, Wolf-Herman</creatorcontrib><creatorcontrib>SAUTES-FRIDMAN, Catherine</creatorcontrib><creatorcontrib>CREMER, Isabelle</creatorcontrib><creatorcontrib>DAMOTTE, Diane</creatorcontrib><creatorcontrib>CROZET, Lucile</creatorcontrib><creatorcontrib>VIEILLARD, Vincent</creatorcontrib><creatorcontrib>VALIDIRE, Pierre</creatorcontrib><creatorcontrib>ANDRE, Pascale</creatorcontrib><creatorcontrib>DIEU-NOSJEAN, Marie-Caroline</creatorcontrib><creatorcontrib>ALIFANO, Marco</creatorcontrib><creatorcontrib>REGNARD, Jean-François</creatorcontrib><title>Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Non-Small-Cell Lung - immunology</subject><subject>Coculture Techniques</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunophenotyping</subject><subject>K562 Cells</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lung Neoplasms - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EotuFnwDyBXFK8cR2xjmuopZWrEoPcI4mjgNBib3YyaH_HkddypGDZc3oe37jN4y9A3EFoM0nIYQptMLyypIvQBQKsH7BdqClKVAp_ZLtnpkLdpnSr1xqEPo1uygBhak17hg9xDCE1fe8CSH2o6fF9fwwLS7SMgafeBj4nV9ytc4h0sTvv_DGTRN_-Ol8WB5PjlNW36zebjwfPT-u_gdvKNrRh5nesFcDTcm9Pd979v3m-ltzWxy_fr5rDsfCaoNL0alalyg6HISgbrAdVgarCsDmU4tKInXoahgqV4HsweUP9LaS2tQlQS_lnn18evcUw-_VpaWdx2TzpORdWFNbCwQDssT_ksZIo1Bmmz3TT6SNIaXohvYUx5niYwui3dbQbhG3W8Rtc7jfutsasu792WHtZtc_q_7mnoEPZ4CSpWmI5O2Y_nFKKYmA8g_Q6Y-v</recordid><startdate>20110815</startdate><enddate>20110815</enddate><creator>PLATONOVA, Sophia</creator><creator>CHERFILS-VICINI, Julien</creator><creator>FRIDMAN, Wolf-Herman</creator><creator>SAUTES-FRIDMAN, Catherine</creator><creator>CREMER, Isabelle</creator><creator>DAMOTTE, Diane</creator><creator>CROZET, Lucile</creator><creator>VIEILLARD, Vincent</creator><creator>VALIDIRE, Pierre</creator><creator>ANDRE, Pascale</creator><creator>DIEU-NOSJEAN, Marie-Caroline</creator><creator>ALIFANO, Marco</creator><creator>REGNARD, Jean-François</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20110815</creationdate><title>Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma</title><author>PLATONOVA, Sophia ; CHERFILS-VICINI, Julien ; FRIDMAN, Wolf-Herman ; SAUTES-FRIDMAN, Catherine ; CREMER, Isabelle ; DAMOTTE, Diane ; CROZET, Lucile ; VIEILLARD, Vincent ; VALIDIRE, Pierre ; ANDRE, Pascale ; DIEU-NOSJEAN, Marie-Caroline ; ALIFANO, Marco ; REGNARD, Jean-François</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-b495270b7f00abfcb76876611c61190637ab7e91f6e613d1e089dc635892a1d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Non-Small-Cell Lung - immunology</topic><topic>Coculture Techniques</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunophenotyping</topic><topic>K562 Cells</topic><topic>Killer Cells, Natural - immunology</topic><topic>Lung Neoplasms - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PLATONOVA, Sophia</creatorcontrib><creatorcontrib>CHERFILS-VICINI, Julien</creatorcontrib><creatorcontrib>FRIDMAN, Wolf-Herman</creatorcontrib><creatorcontrib>SAUTES-FRIDMAN, Catherine</creatorcontrib><creatorcontrib>CREMER, Isabelle</creatorcontrib><creatorcontrib>DAMOTTE, Diane</creatorcontrib><creatorcontrib>CROZET, Lucile</creatorcontrib><creatorcontrib>VIEILLARD, Vincent</creatorcontrib><creatorcontrib>VALIDIRE, Pierre</creatorcontrib><creatorcontrib>ANDRE, Pascale</creatorcontrib><creatorcontrib>DIEU-NOSJEAN, Marie-Caroline</creatorcontrib><creatorcontrib>ALIFANO, Marco</creatorcontrib><creatorcontrib>REGNARD, Jean-François</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PLATONOVA, Sophia</au><au>CHERFILS-VICINI, Julien</au><au>FRIDMAN, Wolf-Herman</au><au>SAUTES-FRIDMAN, Catherine</au><au>CREMER, Isabelle</au><au>DAMOTTE, Diane</au><au>CROZET, Lucile</au><au>VIEILLARD, Vincent</au><au>VALIDIRE, Pierre</au><au>ANDRE, Pascale</au><au>DIEU-NOSJEAN, Marie-Caroline</au><au>ALIFANO, Marco</au><au>REGNARD, Jean-François</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2011-08-15</date><risdate>2011</risdate><volume>71</volume><issue>16</issue><spage>5412</spage><epage>5422</epage><pages>5412-5422</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>21708957</pmid><doi>10.1158/0008-5472.can-10-4179</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2011-08, Vol.71 (16), p.5412-5422 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_907181327 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Aged Aged, 80 and over Antineoplastic agents Biological and medical sciences Carcinoma, Non-Small-Cell Lung - immunology Coculture Techniques Female Flow Cytometry Humans Immunohistochemistry Immunophenotyping K562 Cells Killer Cells, Natural - immunology Lung Neoplasms - immunology Male Medical sciences Middle Aged Pharmacology. Drug treatments Pneumology Tumors Tumors of the respiratory system and mediastinum |
| title | Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T01%3A37%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Profound%20Coordinated%20Alterations%20of%20Intratumoral%20NK%20Cell%20Phenotype%20and%20Function%20in%20Lung%20Carcinoma&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=PLATONOVA,%20Sophia&rft.date=2011-08-15&rft.volume=71&rft.issue=16&rft.spage=5412&rft.epage=5422&rft.pages=5412-5422&rft.issn=0008-5472&rft.eissn=1538-7445&rft.coden=CNREA8&rft_id=info:doi/10.1158/0008-5472.can-10-4179&rft_dat=%3Cproquest_cross%3E907181327%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=883847361&rft_id=info:pmid/21708957&rfr_iscdi=true |