Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host
Tumor growth promotes the expansion of myeloid suppressor cells. An inverse correlation between natural killer (NK) cell activation and myeloid suppressor cell (MSC) expansion in tumor-bearing patients and mice prompted us to investigate the role of MSCs in controlling NK antitumor cytotocixity. Aft...
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| Veröffentlicht in: | Blood 2007-05, Vol.109 (10), p.4336-4342 |
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| creator | Liu, Cunren Yu, Shaohua Kappes, John Wang, Jianhua Grizzle, William E. Zinn, Kurt R. Zhang, Huang-Ge |
| description | Tumor growth promotes the expansion of myeloid suppressor cells. An inverse correlation between natural killer (NK) cell activation and myeloid suppressor cell (MSC) expansion in tumor-bearing patients and mice prompted us to investigate the role of MSCs in controlling NK antitumor cytotocixity. After adoptive transfer to naive recipients, CD11b+Gr-1+ MSCs freshly isolated from spleens of tumor-bearing mice but not naive mice were able to inhibit NK cell cytotoxicity. An in vivo imaging analysis indicates that the removal of tumors resulted in a significant increased ability (P < .05) in NK cell cytotoxicity to eliminate injected YAC-1 cells from the lungs. Fluorescence-activated cell sorter (FACS) analysis of the composition of lung leukocytes further indicates that the removal of tumors also leads to the reduction of MSCs accumulated in the lung. These data suggest that MSCs suppress NK cell cytotoxicity. The inhibition of NK cell cytotoxicity is cell-cell contact dependent. Inhibition of perforin but not granzyme B production was responsible for MSC-mediated inhibition of NK cytotoxicity. Western blot analyses further suggests that MSCs suppress IL-2–mediated NK cell cytotoxicity by affecting the activity of Stat5. |
| doi_str_mv | 10.1182/blood-2006-09-046201 |
| format | Article |
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An inverse correlation between natural killer (NK) cell activation and myeloid suppressor cell (MSC) expansion in tumor-bearing patients and mice prompted us to investigate the role of MSCs in controlling NK antitumor cytotocixity. After adoptive transfer to naive recipients, CD11b+Gr-1+ MSCs freshly isolated from spleens of tumor-bearing mice but not naive mice were able to inhibit NK cell cytotoxicity. An in vivo imaging analysis indicates that the removal of tumors resulted in a significant increased ability (P < .05) in NK cell cytotoxicity to eliminate injected YAC-1 cells from the lungs. Fluorescence-activated cell sorter (FACS) analysis of the composition of lung leukocytes further indicates that the removal of tumors also leads to the reduction of MSCs accumulated in the lung. These data suggest that MSCs suppress NK cell cytotoxicity. The inhibition of NK cell cytotoxicity is cell-cell contact dependent. Inhibition of perforin but not granzyme B production was responsible for MSC-mediated inhibition of NK cytotoxicity. Western blot analyses further suggests that MSCs suppress IL-2–mediated NK cell cytotoxicity by affecting the activity of Stat5.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2006-09-046201</identifier><identifier>PMID: 17244679</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adenocarcinoma - immunology ; Animals ; Biological and medical sciences ; CD11b Antigen - metabolism ; Cell Adhesion - immunology ; Cell Proliferation ; Cells, Cultured ; Cytotoxicity, Immunologic ; Female ; Host-tumor relations. Immunology. Biological markers ; Immunobiology ; Interleukin-2 - pharmacology ; Killer Cells, Natural - immunology ; Mammary Neoplasms, Animal - immunology ; Medical sciences ; Membrane Glycoproteins - metabolism ; Mice ; Mice, Inbred BALB C ; Perforin ; Pore Forming Cytotoxic Proteins - metabolism ; Receptors, Chemokine - metabolism ; Spleen - cytology ; Spleen - drug effects ; STAT5 Transcription Factor - metabolism ; T-Lymphocytes, Regulatory - cytology ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - metabolism ; T-Lymphocytes, Regulatory - physiology ; Tumors</subject><ispartof>Blood, 2007-05, Vol.109 (10), p.4336-4342</ispartof><rights>2007 American Society of Hematology</rights><rights>2007 INIST-CNRS</rights><rights>2007 by The American Society of Hematology 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-2f6ed8163c136fc78142172cc6bfbbad5cd8b5eae3cf46d81cee9e5de9f4b3043</citedby><cites>FETCH-LOGICAL-c557t-2f6ed8163c136fc78142172cc6bfbbad5cd8b5eae3cf46d81cee9e5de9f4b3043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18782408$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17244679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Cunren</creatorcontrib><creatorcontrib>Yu, Shaohua</creatorcontrib><creatorcontrib>Kappes, John</creatorcontrib><creatorcontrib>Wang, Jianhua</creatorcontrib><creatorcontrib>Grizzle, William E.</creatorcontrib><creatorcontrib>Zinn, Kurt R.</creatorcontrib><creatorcontrib>Zhang, Huang-Ge</creatorcontrib><title>Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host</title><title>Blood</title><addtitle>Blood</addtitle><description>Tumor growth promotes the expansion of myeloid suppressor cells. An inverse correlation between natural killer (NK) cell activation and myeloid suppressor cell (MSC) expansion in tumor-bearing patients and mice prompted us to investigate the role of MSCs in controlling NK antitumor cytotocixity. After adoptive transfer to naive recipients, CD11b+Gr-1+ MSCs freshly isolated from spleens of tumor-bearing mice but not naive mice were able to inhibit NK cell cytotoxicity. An in vivo imaging analysis indicates that the removal of tumors resulted in a significant increased ability (P < .05) in NK cell cytotoxicity to eliminate injected YAC-1 cells from the lungs. Fluorescence-activated cell sorter (FACS) analysis of the composition of lung leukocytes further indicates that the removal of tumors also leads to the reduction of MSCs accumulated in the lung. These data suggest that MSCs suppress NK cell cytotoxicity. The inhibition of NK cell cytotoxicity is cell-cell contact dependent. Inhibition of perforin but not granzyme B production was responsible for MSC-mediated inhibition of NK cytotoxicity. Western blot analyses further suggests that MSCs suppress IL-2–mediated NK cell cytotoxicity by affecting the activity of Stat5.</description><subject>Adenocarcinoma - immunology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CD11b Antigen - metabolism</subject><subject>Cell Adhesion - immunology</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Cytotoxicity, Immunologic</subject><subject>Female</subject><subject>Host-tumor relations. Immunology. Biological markers</subject><subject>Immunobiology</subject><subject>Interleukin-2 - pharmacology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Mammary Neoplasms, Animal - immunology</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Perforin</subject><subject>Pore Forming Cytotoxic Proteins - metabolism</subject><subject>Receptors, Chemokine - metabolism</subject><subject>Spleen - cytology</subject><subject>Spleen - drug effects</subject><subject>STAT5 Transcription Factor - metabolism</subject><subject>T-Lymphocytes, Regulatory - cytology</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>T-Lymphocytes, Regulatory - physiology</subject><subject>Tumors</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9P3DAQxS3UCra036CqfOkxxXbsxLkgIQS0AtFLe7ac8RhcZe3IziL225P9oy5cOFnjee_NzI-Qr5z94FyLs35IyVWCsaZiXcVkIxg_IguuhK4YE-wDWbBNU3YtPyGfSvnHGJe1UMfkhLdCyqbtFsRePY82lpAiTZ6WcUCMdLnGIQVHy2ocM5aSMgUchkIzbmss9P52-0VhPaUpPQcI05qGSKfVMuWqR5tDfKCPqUyfyUdvh4Jf9u8p-Xt99efyZ3X3--bX5cVdBUq1UyV8g07zpgZeNx5azaWY1wRoet_31ilwuldosQYvm1kJiB0qh52Xfc1kfUrOd7njql-iA4xTtoMZc1javDbJBvO2E8OjeUhPhmutFKvnALkLgJxKyej_ezkzG-Rmi9xskBvWmR3y2fbt9dyDac94FnzfC2wBO_hsI4Ry0OlWC8n04QCcKT0FzKZAwAjoQkaYjEvh_U1eAFyYpGk</recordid><startdate>20070515</startdate><enddate>20070515</enddate><creator>Liu, Cunren</creator><creator>Yu, Shaohua</creator><creator>Kappes, John</creator><creator>Wang, Jianhua</creator><creator>Grizzle, William E.</creator><creator>Zinn, Kurt R.</creator><creator>Zhang, Huang-Ge</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20070515</creationdate><title>Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host</title><author>Liu, Cunren ; Yu, Shaohua ; Kappes, John ; Wang, Jianhua ; Grizzle, William E. ; Zinn, Kurt R. ; Zhang, Huang-Ge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-2f6ed8163c136fc78142172cc6bfbbad5cd8b5eae3cf46d81cee9e5de9f4b3043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - immunology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>CD11b Antigen - metabolism</topic><topic>Cell Adhesion - immunology</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Cytotoxicity, Immunologic</topic><topic>Female</topic><topic>Host-tumor relations. Immunology. Biological markers</topic><topic>Immunobiology</topic><topic>Interleukin-2 - pharmacology</topic><topic>Killer Cells, Natural - immunology</topic><topic>Mammary Neoplasms, Animal - immunology</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Perforin</topic><topic>Pore Forming Cytotoxic Proteins - metabolism</topic><topic>Receptors, Chemokine - metabolism</topic><topic>Spleen - cytology</topic><topic>Spleen - drug effects</topic><topic>STAT5 Transcription Factor - metabolism</topic><topic>T-Lymphocytes, Regulatory - cytology</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>T-Lymphocytes, Regulatory - physiology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Cunren</creatorcontrib><creatorcontrib>Yu, Shaohua</creatorcontrib><creatorcontrib>Kappes, John</creatorcontrib><creatorcontrib>Wang, Jianhua</creatorcontrib><creatorcontrib>Grizzle, William E.</creatorcontrib><creatorcontrib>Zinn, Kurt R.</creatorcontrib><creatorcontrib>Zhang, Huang-Ge</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Cunren</au><au>Yu, Shaohua</au><au>Kappes, John</au><au>Wang, Jianhua</au><au>Grizzle, William E.</au><au>Zinn, Kurt R.</au><au>Zhang, Huang-Ge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2007-05-15</date><risdate>2007</risdate><volume>109</volume><issue>10</issue><spage>4336</spage><epage>4342</epage><pages>4336-4342</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Tumor growth promotes the expansion of myeloid suppressor cells. An inverse correlation between natural killer (NK) cell activation and myeloid suppressor cell (MSC) expansion in tumor-bearing patients and mice prompted us to investigate the role of MSCs in controlling NK antitumor cytotocixity. After adoptive transfer to naive recipients, CD11b+Gr-1+ MSCs freshly isolated from spleens of tumor-bearing mice but not naive mice were able to inhibit NK cell cytotoxicity. An in vivo imaging analysis indicates that the removal of tumors resulted in a significant increased ability (P < .05) in NK cell cytotoxicity to eliminate injected YAC-1 cells from the lungs. Fluorescence-activated cell sorter (FACS) analysis of the composition of lung leukocytes further indicates that the removal of tumors also leads to the reduction of MSCs accumulated in the lung. These data suggest that MSCs suppress NK cell cytotoxicity. The inhibition of NK cell cytotoxicity is cell-cell contact dependent. Inhibition of perforin but not granzyme B production was responsible for MSC-mediated inhibition of NK cytotoxicity. Western blot analyses further suggests that MSCs suppress IL-2–mediated NK cell cytotoxicity by affecting the activity of Stat5.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>17244679</pmid><doi>10.1182/blood-2006-09-046201</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - immunology Animals Biological and medical sciences CD11b Antigen - metabolism Cell Adhesion - immunology Cell Proliferation Cells, Cultured Cytotoxicity, Immunologic Female Host-tumor relations. Immunology. Biological markers Immunobiology Interleukin-2 - pharmacology Killer Cells, Natural - immunology Mammary Neoplasms, Animal - immunology Medical sciences Membrane Glycoproteins - metabolism Mice Mice, Inbred BALB C Perforin Pore Forming Cytotoxic Proteins - metabolism Receptors, Chemokine - metabolism Spleen - cytology Spleen - drug effects STAT5 Transcription Factor - metabolism T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - physiology Tumors |
| title | Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host |
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