Treatment with lenalidomide induces immunoactivating and counter‐regulatory immunosuppressive changes in myeloma patients
Summary Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was ass...
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| Veröffentlicht in: | Clinical and experimental immunology 2014-08, Vol.177 (2), p.439-453 |
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| creator | Busch, A. Zeh, D. Janzen, V. Mügge, L.‐O. Wolf, D. Fingerhut, L. Hahn‐Ast, C. Maurer, O. Brossart, P. Lilienfeld‐Toal, M. |
| description | Summary
Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti‐tumour response. In addition, lenalidomide‐treated patients showed higher abundance of CD14+ myeloid cells co‐expressing CD15. This population was able to inhibit both CD4+ and CD8+ T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid‐derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14+CD15+ MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter‐regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide. |
| doi_str_mv | 10.1111/cei.12343 |
| format | Article |
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Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti‐tumour response. In addition, lenalidomide‐treated patients showed higher abundance of CD14+ myeloid cells co‐expressing CD15. This population was able to inhibit both CD4+ and CD8+ T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid‐derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14+CD15+ MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter‐regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/cei.12343</identifier><identifier>PMID: 24712857</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Aged ; Bone marrow ; Female ; Humans ; Immune system ; Immunologic Factors - pharmacology ; Immunologic Factors - therapeutic use ; Immunologic Memory - immunology ; Immunomodulation - drug effects ; Immunophenotyping ; immunoregulation ; lenalidomide ; Lymphocyte Activation - immunology ; Lymphocytes ; Male ; MDSCs ; Middle Aged ; multiple myeloma ; Multiple Myeloma - drug therapy ; Multiple Myeloma - immunology ; Multiple Myeloma - pathology ; Myeloid Cells - drug effects ; Myeloid Cells - immunology ; Myeloid Cells - metabolism ; Original ; Phenotype ; T cells ; T-Lymphocyte Subsets - drug effects ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; Thalidomide - analogs & derivatives ; Thalidomide - pharmacology ; Thalidomide - therapeutic use</subject><ispartof>Clinical and experimental immunology, 2014-08, Vol.177 (2), p.439-453</ispartof><rights>2014 British Society for Immunology</rights><rights>2014 British Society for Immunology.</rights><rights>Copyright © 2014 British Society for Immunology</rights><rights>2014 British Society for Immunology 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4763-9bb9566abb6835b2e91beb56369414abae726195d4a24e6d03aa029404f3f6813</citedby><cites>FETCH-LOGICAL-c4763-9bb9566abb6835b2e91beb56369414abae726195d4a24e6d03aa029404f3f6813</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/PMC4226595/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226595/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24712857$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Busch, A.</creatorcontrib><creatorcontrib>Zeh, D.</creatorcontrib><creatorcontrib>Janzen, V.</creatorcontrib><creatorcontrib>Mügge, L.‐O.</creatorcontrib><creatorcontrib>Wolf, D.</creatorcontrib><creatorcontrib>Fingerhut, L.</creatorcontrib><creatorcontrib>Hahn‐Ast, C.</creatorcontrib><creatorcontrib>Maurer, O.</creatorcontrib><creatorcontrib>Brossart, P.</creatorcontrib><creatorcontrib>Lilienfeld‐Toal, M.</creatorcontrib><title>Treatment with lenalidomide induces immunoactivating and counter‐regulatory immunosuppressive changes in myeloma patients</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Summary
Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti‐tumour response. In addition, lenalidomide‐treated patients showed higher abundance of CD14+ myeloid cells co‐expressing CD15. This population was able to inhibit both CD4+ and CD8+ T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid‐derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14+CD15+ MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter‐regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.</description><subject>Aged</subject><subject>Bone marrow</subject><subject>Female</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunologic Factors - pharmacology</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Immunologic Memory - immunology</subject><subject>Immunomodulation - drug effects</subject><subject>Immunophenotyping</subject><subject>immunoregulation</subject><subject>lenalidomide</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>MDSCs</subject><subject>Middle Aged</subject><subject>multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - immunology</subject><subject>Multiple Myeloma - pathology</subject><subject>Myeloid Cells - drug effects</subject><subject>Myeloid Cells - immunology</subject><subject>Myeloid Cells - metabolism</subject><subject>Original</subject><subject>Phenotype</subject><subject>T cells</subject><subject>T-Lymphocyte Subsets - drug effects</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>Thalidomide - analogs & derivatives</subject><subject>Thalidomide - pharmacology</subject><subject>Thalidomide - therapeutic use</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd9qFDEUh4Modq1e-AIy4I1eTJt_k5ncCLJULRS8qdfhzMzZ3ZSZZEwmWxZvfIQ-Y5_EbHctKhgC4ZCP7xzOj5DXjJ6xfM47tGeMCymekAUTqio5l_opWVBKdakZlSfkRYw3uVRK8efkhMua8aaqF-THdUCYR3RzcWvnTTGgg8H2frQ9Ftb1qcNY2HFMzkM32y3M1q0LcH3R-eRmDPc_7wKu0wCzD7sjGdM0BYzRbrHoNuDWe4crxh0OfoRiypLcML4kz1YwRHx1fE_Jt08X18sv5dXXz5fLj1dlJ2slSt22ulIK2lY1omo5atZiWymhtGQSWsCaK6arXgKXqHoqACjXksqVWKmGiVPy4eCdUjti3-XeAQYzBTtC2BkP1vz94-zGrP3WSM5VpasseHcUBP89YZzNaGOHwwAOfYqGVbJu8m326Nt_0BufQt7pAyUUZUrSTL0_UF3wMQZcPQ7DqNlHanKk5iHSzL75c_pH8neGGTg_ALd2wN3_TWZ5cXlQ_gKABK-e</recordid><startdate>201408</startdate><enddate>201408</enddate><creator>Busch, A.</creator><creator>Zeh, D.</creator><creator>Janzen, V.</creator><creator>Mügge, L.‐O.</creator><creator>Wolf, D.</creator><creator>Fingerhut, L.</creator><creator>Hahn‐Ast, C.</creator><creator>Maurer, O.</creator><creator>Brossart, P.</creator><creator>Lilienfeld‐Toal, M.</creator><general>Oxford University Press</general><general>Blackwell Science Inc</general><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>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>5PM</scope></search><sort><creationdate>201408</creationdate><title>Treatment with lenalidomide induces immunoactivating and counter‐regulatory immunosuppressive changes in myeloma patients</title><author>Busch, A. ; Zeh, D. ; Janzen, V. ; Mügge, L.‐O. ; Wolf, D. ; Fingerhut, L. ; Hahn‐Ast, C. ; Maurer, O. ; Brossart, P. ; Lilienfeld‐Toal, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4763-9bb9566abb6835b2e91beb56369414abae726195d4a24e6d03aa029404f3f6813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Bone marrow</topic><topic>Female</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunologic Factors - pharmacology</topic><topic>Immunologic Factors - therapeutic use</topic><topic>Immunologic Memory - immunology</topic><topic>Immunomodulation - drug effects</topic><topic>Immunophenotyping</topic><topic>immunoregulation</topic><topic>lenalidomide</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>MDSCs</topic><topic>Middle Aged</topic><topic>multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - immunology</topic><topic>Multiple Myeloma - pathology</topic><topic>Myeloid Cells - drug effects</topic><topic>Myeloid Cells - immunology</topic><topic>Myeloid Cells - metabolism</topic><topic>Original</topic><topic>Phenotype</topic><topic>T cells</topic><topic>T-Lymphocyte Subsets - drug effects</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>Thalidomide - analogs & derivatives</topic><topic>Thalidomide - pharmacology</topic><topic>Thalidomide - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Busch, A.</creatorcontrib><creatorcontrib>Zeh, D.</creatorcontrib><creatorcontrib>Janzen, V.</creatorcontrib><creatorcontrib>Mügge, L.‐O.</creatorcontrib><creatorcontrib>Wolf, D.</creatorcontrib><creatorcontrib>Fingerhut, L.</creatorcontrib><creatorcontrib>Hahn‐Ast, C.</creatorcontrib><creatorcontrib>Maurer, O.</creatorcontrib><creatorcontrib>Brossart, P.</creatorcontrib><creatorcontrib>Lilienfeld‐Toal, M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Busch, A.</au><au>Zeh, D.</au><au>Janzen, V.</au><au>Mügge, L.‐O.</au><au>Wolf, D.</au><au>Fingerhut, L.</au><au>Hahn‐Ast, C.</au><au>Maurer, O.</au><au>Brossart, P.</au><au>Lilienfeld‐Toal, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment with lenalidomide induces immunoactivating and counter‐regulatory immunosuppressive changes in myeloma patients</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2014-08</date><risdate>2014</risdate><volume>177</volume><issue>2</issue><spage>439</spage><epage>453</epage><pages>439-453</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><abstract>Summary
Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti‐tumour response. In addition, lenalidomide‐treated patients showed higher abundance of CD14+ myeloid cells co‐expressing CD15. This population was able to inhibit both CD4+ and CD8+ T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid‐derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14+CD15+ MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter‐regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>24712857</pmid><doi>10.1111/cei.12343</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Bone marrow Female Humans Immune system Immunologic Factors - pharmacology Immunologic Factors - therapeutic use Immunologic Memory - immunology Immunomodulation - drug effects Immunophenotyping immunoregulation lenalidomide Lymphocyte Activation - immunology Lymphocytes Male MDSCs Middle Aged multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - immunology Multiple Myeloma - pathology Myeloid Cells - drug effects Myeloid Cells - immunology Myeloid Cells - metabolism Original Phenotype T cells T-Lymphocyte Subsets - drug effects T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Thalidomide - analogs & derivatives Thalidomide - pharmacology Thalidomide - therapeutic use |
| title | Treatment with lenalidomide induces immunoactivating and counter‐regulatory immunosuppressive changes in myeloma patients |
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