Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
Regulatory T (T reg ) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen–reactive lymphocytes mediated by T reg cells; however, definitive evidence that T reg cell...
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Veröffentlicht in: | Nature medicine 2004-09, Vol.10 (9), p.942-949 |
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creator | Zou, Weiping Curiel, Tyler J Coukos, George Zou, Linhua Alvarez, Xavier Cheng, Pui Mottram, Peter Evdemon-Hogan, Melina Conejo-Garcia, Jose R Zhang, Lin Burow, Matthew Zhu, Yun Wei, Shuang Kryczek, Ilona Daniel, Ben Gordon, Alan Myers, Leann Lackner, Andrew Disis, Mary L Knutson, Keith L Chen, Lieping |
description | Regulatory T (T
reg
) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen–reactive lymphocytes mediated by T
reg
cells; however, definitive evidence that T
reg
cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4
+
CD25
+
FOXP3
+
T
reg
cells in 104 individuals affected with ovarian carcinoma, that human tumor T
reg
cells suppress tumor-specific T cell immunity and contribute to growth of human tumors
in vivo
. We also show that tumor T
reg
cells are associated with a high death hazard and reduced survival. Human T
reg
cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T
reg
cells to the tumor. This specific recruitment of T
reg
cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T
reg
cell migration or function may help to defeat human cancer. |
doi_str_mv | 10.1038/nm1093 |
format | Article |
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reg
) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen–reactive lymphocytes mediated by T
reg
cells; however, definitive evidence that T
reg
cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4
+
CD25
+
FOXP3
+
T
reg
cells in 104 individuals affected with ovarian carcinoma, that human tumor T
reg
cells suppress tumor-specific T cell immunity and contribute to growth of human tumors
in vivo
. We also show that tumor T
reg
cells are associated with a high death hazard and reduced survival. Human T
reg
cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T
reg
cells to the tumor. This specific recruitment of T
reg
cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T
reg
cell migration or function may help to defeat human cancer.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm1093</identifier><identifier>PMID: 15322536</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animals ; Ascites - immunology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; CD4-Positive T-Lymphocytes ; Cell Movement - immunology ; Chemokine CCL22 ; Chemokines, CC - immunology ; Chemokines, CC - metabolism ; Dendritic Cells - immunology ; DNA-Binding Proteins ; Female ; Forkhead Transcription Factors ; Humans ; Immunity, Cellular - immunology ; Immunophenotyping ; Infectious Diseases ; Lymph nodes ; Lymphocyte Activation - immunology ; Lymphocytes ; Metabolic Diseases ; Mice ; Microscopy, Confocal - methods ; Molecular Medicine ; Neurosciences ; Ovarian cancer ; Ovarian Neoplasms - immunology ; Receptors, Interleukin-2 ; T-Lymphocytes - immunology ; Tumors</subject><ispartof>Nature medicine, 2004-09, Vol.10 (9), p.942-949</ispartof><rights>Springer Nature America, Inc. 2004</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-4db44919e076c333d692f0dbd599d26ffc71b171707e3bfc262a644b7431f2403</citedby><cites>FETCH-LOGICAL-c562t-4db44919e076c333d692f0dbd599d26ffc71b171707e3bfc262a644b7431f2403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15322536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zou, Weiping</creatorcontrib><creatorcontrib>Curiel, Tyler J</creatorcontrib><creatorcontrib>Coukos, George</creatorcontrib><creatorcontrib>Zou, Linhua</creatorcontrib><creatorcontrib>Alvarez, Xavier</creatorcontrib><creatorcontrib>Cheng, Pui</creatorcontrib><creatorcontrib>Mottram, Peter</creatorcontrib><creatorcontrib>Evdemon-Hogan, Melina</creatorcontrib><creatorcontrib>Conejo-Garcia, Jose R</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Burow, Matthew</creatorcontrib><creatorcontrib>Zhu, Yun</creatorcontrib><creatorcontrib>Wei, Shuang</creatorcontrib><creatorcontrib>Kryczek, Ilona</creatorcontrib><creatorcontrib>Daniel, Ben</creatorcontrib><creatorcontrib>Gordon, Alan</creatorcontrib><creatorcontrib>Myers, Leann</creatorcontrib><creatorcontrib>Lackner, Andrew</creatorcontrib><creatorcontrib>Disis, Mary L</creatorcontrib><creatorcontrib>Knutson, Keith L</creatorcontrib><creatorcontrib>Chen, Lieping</creatorcontrib><title>Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Regulatory T (T
reg
) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen–reactive lymphocytes mediated by T
reg
cells; however, definitive evidence that T
reg
cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4
+
CD25
+
FOXP3
+
T
reg
cells in 104 individuals affected with ovarian carcinoma, that human tumor T
reg
cells suppress tumor-specific T cell immunity and contribute to growth of human tumors
in vivo
. We also show that tumor T
reg
cells are associated with a high death hazard and reduced survival. Human T
reg
cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T
reg
cells to the tumor. This specific recruitment of T
reg
cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T
reg
cell migration or function may help to defeat human cancer.</description><subject>Animals</subject><subject>Ascites - immunology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>CD4-Positive T-Lymphocytes</subject><subject>Cell Movement - immunology</subject><subject>Chemokine CCL22</subject><subject>Chemokines, CC - immunology</subject><subject>Chemokines, CC - metabolism</subject><subject>Dendritic Cells - immunology</subject><subject>DNA-Binding Proteins</subject><subject>Female</subject><subject>Forkhead Transcription Factors</subject><subject>Humans</subject><subject>Immunity, Cellular - immunology</subject><subject>Immunophenotyping</subject><subject>Infectious Diseases</subject><subject>Lymph nodes</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Microscopy, Confocal - methods</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Receptors, Interleukin-2</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumors</subject><issn>1078-8956</issn><issn>1546-170X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0t1r1TAUAPAiiptX_QtEgg8THzrz0aa3j2P4MRgM3BTfSpqcdBltcpeP4v57c-nFOb2g9KEN53dOOKenKF4SfEwwW7-3E8Ete1QckrriJWnw98f5Gzfrct3W_KB4FsINxpjhun1aHJCaUVozfljMlxuQRhuJPEifTJzARuR0Pg5pFNH5O3SFJIxjQMYiNwtvhEVSeGmsmwTSLkTwOThNyQLaeDObEQZAwqp8AmVkDLmaShIUCsnPZhbj8-KJFmOAF7v3qvj68cPV6efy_OLT2enJeSlrTmNZqb6qWtICbrhkjCneUo1Vr-q2VZRrLRvSkya32wDrtaScCl5VfVMxommF2ao4WupuvLtNEGI3mbDtRlhwKXScr1lDKvZPSNaYct7WGb75A9645G1uoqOUEUIY315bLmgQI3TGahe9kANY8GJ0FnQeUXdCWkYx5zllVRzv8flRMBm5N-Hdg4RsIvyIg0ghdGeXX_7fXnx7aI9-s9cgxngd3JiicTbshdK7EDzoLv_5Sfi7juBuu5HdspEZvt7NK_UTqHu2W8EM3i4g5JAdwN8P9K9SrxZpRUwefpXahX8ChHzvMQ</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Zou, 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recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival</title><author>Zou, Weiping ; Curiel, Tyler J ; Coukos, George ; Zou, Linhua ; Alvarez, Xavier ; Cheng, Pui ; Mottram, Peter ; Evdemon-Hogan, Melina ; Conejo-Garcia, Jose R ; Zhang, Lin ; Burow, Matthew ; Zhu, Yun ; Wei, Shuang ; Kryczek, Ilona ; Daniel, Ben ; Gordon, Alan ; Myers, Leann ; Lackner, Andrew ; Disis, Mary L ; Knutson, Keith L ; Chen, Lieping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-4db44919e076c333d692f0dbd599d26ffc71b171707e3bfc262a644b7431f2403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Ascites - immunology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>CD4-Positive T-Lymphocytes</topic><topic>Cell Movement - immunology</topic><topic>Chemokine CCL22</topic><topic>Chemokines, CC - immunology</topic><topic>Chemokines, CC - metabolism</topic><topic>Dendritic Cells - immunology</topic><topic>DNA-Binding Proteins</topic><topic>Female</topic><topic>Forkhead Transcription Factors</topic><topic>Humans</topic><topic>Immunity, Cellular - immunology</topic><topic>Immunophenotyping</topic><topic>Infectious Diseases</topic><topic>Lymph nodes</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Metabolic Diseases</topic><topic>Mice</topic><topic>Microscopy, Confocal - methods</topic><topic>Molecular Medicine</topic><topic>Neurosciences</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - immunology</topic><topic>Receptors, Interleukin-2</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zou, Weiping</creatorcontrib><creatorcontrib>Curiel, Tyler J</creatorcontrib><creatorcontrib>Coukos, 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L</au><au>Chen, Lieping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2004-09-01</date><risdate>2004</risdate><volume>10</volume><issue>9</issue><spage>942</spage><epage>949</epage><pages>942-949</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Regulatory T (T
reg
) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen–reactive lymphocytes mediated by T
reg
cells; however, definitive evidence that T
reg
cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4
+
CD25
+
FOXP3
+
T
reg
cells in 104 individuals affected with ovarian carcinoma, that human tumor T
reg
cells suppress tumor-specific T cell immunity and contribute to growth of human tumors
in vivo
. We also show that tumor T
reg
cells are associated with a high death hazard and reduced survival. Human T
reg
cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T
reg
cells to the tumor. This specific recruitment of T
reg
cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T
reg
cell migration or function may help to defeat human cancer.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>15322536</pmid><doi>10.1038/nm1093</doi><tpages>8</tpages></addata></record> |
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language | eng |
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source | MEDLINE; Nature; Alma/SFX Local Collection |
subjects | Animals Ascites - immunology Biomedical and Life Sciences Biomedicine Cancer Research CD4-Positive T-Lymphocytes Cell Movement - immunology Chemokine CCL22 Chemokines, CC - immunology Chemokines, CC - metabolism Dendritic Cells - immunology DNA-Binding Proteins Female Forkhead Transcription Factors Humans Immunity, Cellular - immunology Immunophenotyping Infectious Diseases Lymph nodes Lymphocyte Activation - immunology Lymphocytes Metabolic Diseases Mice Microscopy, Confocal - methods Molecular Medicine Neurosciences Ovarian cancer Ovarian Neoplasms - immunology Receptors, Interleukin-2 T-Lymphocytes - immunology Tumors |
title | Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival |
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