Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy
Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only fe...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2009-01, Vol.58 (1), p.49-59 |
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| creator | Diaz-Montero, C. Marcela Salem, Mohamed Labib Nishimura, Michael I. Garrett-Mayer, Elizabeth Cole, David J. Montero, Alberto J. |
| description | Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I–IV). Percentages of circulating MDSC (Lin
−/Lo
, HLA DR−, CD33
+
CD11b
+
) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin–cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials. |
| doi_str_mv | 10.1007/s00262-008-0523-4 |
| format | Article |
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−/Lo
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) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin–cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-008-0523-4</identifier><identifier>PMID: 18446337</identifier><identifier>CODEN: CIIMDN</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adult ; Aged ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - immunology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - immunology ; Breast Neoplasms - physiopathology ; Cancer Research ; Cancer therapies ; Chemotherapy ; Cyclophosphamide - immunology ; Cyclophosphamide - therapeutic use ; Disease Progression ; Doxorubicin - immunology ; Doxorubicin - therapeutic use ; Female ; Flow Cytometry ; Gynecology. Andrology. Obstetrics ; Humans ; Immunology ; Immunotherapy ; Lymphocytes ; Male ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Metastasis ; Middle Aged ; Myeloid Cells - cytology ; Myeloid Cells - immunology ; Neoplasm Staging ; Oncology ; Original Article ; Patients ; Pharmacology. Drug treatments ; Reference Standards ; Tumor Burden - immunology ; Tumors</subject><ispartof>Cancer Immunology, Immunotherapy, 2009-01, Vol.58 (1), p.49-59</ispartof><rights>Springer-Verlag 2008</rights><rights>2009 INIST-CNRS</rights><rights>Springer-Verlag 2009</rights><rights>Springer-Verlag 2008 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-4f98313cc38029cde7d9ace839fcc68381e4656dfa3033113d53a708aa6e219f3</citedby><cites>FETCH-LOGICAL-c528t-4f98313cc38029cde7d9ace839fcc68381e4656dfa3033113d53a708aa6e219f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401888/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401888/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,41486,42555,51317,53789,53791</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21046928$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18446337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Diaz-Montero, C. Marcela</creatorcontrib><creatorcontrib>Salem, Mohamed Labib</creatorcontrib><creatorcontrib>Nishimura, Michael I.</creatorcontrib><creatorcontrib>Garrett-Mayer, Elizabeth</creatorcontrib><creatorcontrib>Cole, David J.</creatorcontrib><creatorcontrib>Montero, Alberto J.</creatorcontrib><title>Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I–IV). Percentages of circulating MDSC (Lin
−/Lo
, HLA DR−, CD33
+
CD11b
+
) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin–cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - immunology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - physiopathology</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Cyclophosphamide - immunology</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Disease Progression</subject><subject>Doxorubicin - immunology</subject><subject>Doxorubicin - therapeutic use</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gynecology. Andrology. 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Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Myeloid Cells - cytology</topic><topic>Myeloid Cells - immunology</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Patients</topic><topic>Pharmacology. Drug treatments</topic><topic>Reference Standards</topic><topic>Tumor Burden - immunology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Diaz-Montero, C. Marcela</creatorcontrib><creatorcontrib>Salem, Mohamed Labib</creatorcontrib><creatorcontrib>Nishimura, Michael I.</creatorcontrib><creatorcontrib>Garrett-Mayer, Elizabeth</creatorcontrib><creatorcontrib>Cole, David J.</creatorcontrib><creatorcontrib>Montero, Alberto J.</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>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Diaz-Montero, C. Marcela</au><au>Salem, Mohamed Labib</au><au>Nishimura, Michael I.</au><au>Garrett-Mayer, Elizabeth</au><au>Cole, David J.</au><au>Montero, Alberto J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>58</volume><issue>1</issue><spage>49</spage><epage>59</epage><pages>49-59</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><coden>CIIMDN</coden><abstract>Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I–IV). Percentages of circulating MDSC (Lin
−/Lo
, HLA DR−, CD33
+
CD11b
+
) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin–cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>18446337</pmid><doi>10.1007/s00262-008-0523-4</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer Immunology, Immunotherapy, 2009-01, Vol.58 (1), p.49-59 |
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| language | eng |
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| subjects | Adult Aged Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - immunology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - physiopathology Cancer Research Cancer therapies Chemotherapy Cyclophosphamide - immunology Cyclophosphamide - therapeutic use Disease Progression Doxorubicin - immunology Doxorubicin - therapeutic use Female Flow Cytometry Gynecology. Andrology. Obstetrics Humans Immunology Immunotherapy Lymphocytes Male Mammary gland diseases Medical sciences Medicine Medicine & Public Health Metastasis Middle Aged Myeloid Cells - cytology Myeloid Cells - immunology Neoplasm Staging Oncology Original Article Patients Pharmacology. Drug treatments Reference Standards Tumor Burden - immunology Tumors |
| title | Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy |
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