Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice
Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8$^+$ T cells with impai...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1992-12, Vol.258 (5089), p.1795-1798 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Mizoguchi, Hiromoto O'Shea, John J. Longo, Dan L. Loeffler, Cynthia M. McVicar, Daniel W. Ochoa, Augusto C. |
| description | Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8$^+$ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-α and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3γ and completely lacked CD3ζ, which was replaced by the Fc$_\epsilon$ γ-chain. Expression of the tyrosine kinases p56$^{lck}$ and p59$^{fyn}$ was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts. |
| doi_str_mv | 10.1126/science.1465616 |
| format | Article |
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In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8$^+$ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-α and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3γ and completely lacked CD3ζ, which was replaced by the Fc$_\epsilon$ γ-chain. Expression of the tyrosine kinases p56$^{lck}$ and p59$^{fyn}$ was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1465616</identifier><identifier>PMID: 1465616</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Animals ; Antibodies ; Antigen receptors, T cell ; Biological and medical sciences ; Calcium - metabolism ; Cancer ; Causes of ; CD3 Complex - metabolism ; CD8 Antigens - analysis ; Cell lines ; Colonic Neoplasms - immunology ; Cytotoxicity, Immunologic ; Fluorescence ; Granzymes ; Host-tumor relations. Immunology. Biological markers ; Immunodeficiency ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Macromolecular Substances ; Medical sciences ; Mice ; Molecules ; Phosphorylation ; Physiological aspects ; Protein-Tyrosine Kinases - metabolism ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-fyn ; Receptors ; Receptors, Antigen, T-Cell - isolation & purification ; Receptors, Antigen, T-Cell - metabolism ; Receptors, IgG - metabolism ; Serine Endopeptidases - biosynthesis ; Serine Endopeptidases - genetics ; Signal Transduction ; T cell antigen receptors ; T cells ; T lymphocytes ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes - immunology ; T-Lymphocytes - physiology ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - genetics ; Tumors</subject><ispartof>Science (American Association for the Advancement of Science), 1992-12, Vol.258 (5089), p.1795-1798</ispartof><rights>Copyright 1992 American Association for the Advancement of Science</rights><rights>1993 INIST-CNRS</rights><rights>COPYRIGHT 1992 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1992 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-9e57bc730d5e6de26a1499072c6181b7d7af288c4e0b26a0b5f04f46dc813d493</citedby><cites>FETCH-LOGICAL-c563t-9e57bc730d5e6de26a1499072c6181b7d7af288c4e0b26a0b5f04f46dc813d493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2880384$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2880384$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4554942$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1465616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mizoguchi, Hiromoto</creatorcontrib><creatorcontrib>O'Shea, John J.</creatorcontrib><creatorcontrib>Longo, Dan L.</creatorcontrib><creatorcontrib>Loeffler, Cynthia M.</creatorcontrib><creatorcontrib>McVicar, Daniel W.</creatorcontrib><creatorcontrib>Ochoa, Augusto C.</creatorcontrib><title>Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8$^+$ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-α and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3γ and completely lacked CD3ζ, which was replaced by the Fc$_\epsilon$ γ-chain. Expression of the tyrosine kinases p56$^{lck}$ and p59$^{fyn}$ was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antigen receptors, T cell</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cancer</subject><subject>Causes of</subject><subject>CD3 Complex - metabolism</subject><subject>CD8 Antigens - analysis</subject><subject>Cell lines</subject><subject>Colonic Neoplasms - immunology</subject><subject>Cytotoxicity, Immunologic</subject><subject>Fluorescence</subject><subject>Granzymes</subject><subject>Host-tumor relations. Immunology. Biological markers</subject><subject>Immunodeficiency</subject><subject>Lymphocyte Specific Protein Tyrosine Kinase p56(lck)</subject><subject>Macromolecular Substances</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Molecules</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-fyn</subject><subject>Receptors</subject><subject>Receptors, Antigen, T-Cell - isolation & purification</subject><subject>Receptors, Antigen, T-Cell - metabolism</subject><subject>Receptors, IgG - metabolism</subject><subject>Serine Endopeptidases - biosynthesis</subject><subject>Serine Endopeptidases - genetics</subject><subject>Signal Transduction</subject><subject>T cell antigen receptors</subject><subject>T cells</subject><subject>T lymphocytes</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - physiology</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumors</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0s1r2zAYBnAzNrqs23mXDXwYY4e6lawPW8c0dFkhXQ5NdzWK_NpTkaVUsmH576suJiMQWNDB8D4_C-P3SZKPGF1inPOroDRYBZeYcsYxf5VMMBIsEzkir5MJQoRnJSrY2-RdCI8IxUyQs-Rs5JPkYWp68LLXzoZU2_Ret1aadOWlDfWgXubpnTOgBgN_wSpdbLvNb6e2fRw03nXpauicz65Bem3b9E4reJ-8aaQJ8GF8nicP329Wsx_ZYjm_nU0XmWKc9JkAVqxVQVDNgNeQc4mpEKjIFcclXhd1IZu8LBUFtI4hWrMG0YbyWpWY1FSQ8-Tr7t6Nd08DhL7qdFBgjLTghlAVhAhaCP5fiDkpGSpohBc72EoDlbaN671ULdj4k4yz0Og4nmKCGI2fGnl2hMdTQ6fVMf_twEfSw5--lUMI1e39z5Pp8tfJ9Hp-Ki3niwN6cYwqZwy0UMVFzpYH_GrHlXcheGiqjded9NsKo-qlq9XY1WosX3zj87iUYd1B_c_v8y9jLoOSpomdVDrsGWWMCppH9mnHHkPv_D6OxUGkpOQZCkP25A</recordid><startdate>19921211</startdate><enddate>19921211</enddate><creator>Mizoguchi, Hiromoto</creator><creator>O'Shea, John J.</creator><creator>Longo, Dan L.</creator><creator>Loeffler, Cynthia M.</creator><creator>McVicar, Daniel W.</creator><creator>Ochoa, Augusto C.</creator><general>American Society for the Advancement of Science</general><general>American Association for the Advancement of Science</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>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19921211</creationdate><title>Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice</title><author>Mizoguchi, Hiromoto ; O'Shea, John J. ; Longo, Dan L. ; Loeffler, Cynthia M. ; McVicar, Daniel W. ; Ochoa, Augusto C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-9e57bc730d5e6de26a1499072c6181b7d7af288c4e0b26a0b5f04f46dc813d493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antigen receptors, T cell</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cancer</topic><topic>Causes of</topic><topic>CD3 Complex - metabolism</topic><topic>CD8 Antigens - analysis</topic><topic>Cell lines</topic><topic>Colonic Neoplasms - immunology</topic><topic>Cytotoxicity, Immunologic</topic><topic>Fluorescence</topic><topic>Granzymes</topic><topic>Host-tumor relations. Immunology. Biological markers</topic><topic>Immunodeficiency</topic><topic>Lymphocyte Specific Protein Tyrosine Kinase p56(lck)</topic><topic>Macromolecular Substances</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Molecules</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-fyn</topic><topic>Receptors</topic><topic>Receptors, Antigen, T-Cell - isolation & purification</topic><topic>Receptors, Antigen, T-Cell - metabolism</topic><topic>Receptors, IgG - metabolism</topic><topic>Serine Endopeptidases - biosynthesis</topic><topic>Serine Endopeptidases - genetics</topic><topic>Signal Transduction</topic><topic>T cell antigen receptors</topic><topic>T cells</topic><topic>T lymphocytes</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - physiology</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mizoguchi, Hiromoto</creatorcontrib><creatorcontrib>O'Shea, John J.</creatorcontrib><creatorcontrib>Longo, Dan L.</creatorcontrib><creatorcontrib>Loeffler, Cynthia M.</creatorcontrib><creatorcontrib>McVicar, Daniel W.</creatorcontrib><creatorcontrib>Ochoa, Augusto C.</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>Gale In Context: High School</collection><collection>Gale In Context: Biography</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mizoguchi, Hiromoto</au><au>O'Shea, John J.</au><au>Longo, Dan L.</au><au>Loeffler, Cynthia M.</au><au>McVicar, Daniel W.</au><au>Ochoa, Augusto C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>1992-12-11</date><risdate>1992</risdate><volume>258</volume><issue>5089</issue><spage>1795</spage><epage>1798</epage><pages>1795-1798</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8$^+$ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-α and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3γ and completely lacked CD3ζ, which was replaced by the Fc$_\epsilon$ γ-chain. Expression of the tyrosine kinases p56$^{lck}$ and p59$^{fyn}$ was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>1465616</pmid><doi>10.1126/science.1465616</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1992-12, Vol.258 (5089), p.1795-1798 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | Jstor Complete Legacy; MEDLINE; Science Magazine |
| subjects | Animals Antibodies Antigen receptors, T cell Biological and medical sciences Calcium - metabolism Cancer Causes of CD3 Complex - metabolism CD8 Antigens - analysis Cell lines Colonic Neoplasms - immunology Cytotoxicity, Immunologic Fluorescence Granzymes Host-tumor relations. Immunology. Biological markers Immunodeficiency Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Macromolecular Substances Medical sciences Mice Molecules Phosphorylation Physiological aspects Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-fyn Receptors Receptors, Antigen, T-Cell - isolation & purification Receptors, Antigen, T-Cell - metabolism Receptors, IgG - metabolism Serine Endopeptidases - biosynthesis Serine Endopeptidases - genetics Signal Transduction T cell antigen receptors T cells T lymphocytes T-Lymphocyte Subsets - immunology T-Lymphocytes - immunology T-Lymphocytes - physiology Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics Tumors |
| title | Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice |
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