The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib
Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant c...
Gespeichert in:
Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2016-03, Vol.65 (3), p.273-282 |
---|---|
Hauptverfasser: | , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 282 |
---|---|
container_issue | 3 |
container_start_page | 273 |
container_title | Cancer Immunology, Immunotherapy |
container_volume | 65 |
creator | Heine, Annkristin Schilling, Judith Grünwald, Barbara Krüger, Achim Gevensleben, Heidrun Held, Stefanie Andrea Erika Garbi, Natalio Kurts, Christian Brossart, Peter Knolle, Percy Diehl, Linda Höchst, Bastian |
description | Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant cell clone itself but also affect immune cells. Here, we investigate the effect of TKIs on the induction of MDSCs that differentiate from mature human monocytes using a new in vitro model of MDSC induction through activated hepatic stellate cells (HSCs). We show that frequencies of monocytic CD14
+
HLA-DR
−/low
MDSCs derived from mature monocytes were significantly and dose-dependently reduced in the presence of dasatinib, nilotinib and sorafenib, whereas sunitinib had no effect. These regulatory effects were only observed when TKIs were present during the early induction phase of MDSCs through activated HSCs, whereas already differentiated MDSCs were not further influenced by TKIs. Neither the MAPK nor the NFκB pathway was modulated in MDSCs when any of the TKIs was applied. When functional analyses were performed, we found that myeloid cells treated with sorafenib, nilotinib or dasatinib, but not sunitinib, displayed decreased suppressive capacity with regard to CD8
+
T cell proliferation. Our results indicate that sorafenib, nilotinib and dasatinib, but not sunitinib, decrease the HSC-mediated differentiation of monocytes into functional MDSCs. Therefore, treatment of cancer patients with these TKIs may in addition to having a direct effect on cancer cells also prevent the differentiation of monocytes into MDSCs and thereby differentially modulate the success of immunotherapeutic or other anti-cancer approaches. |
doi_str_mv | 10.1007/s00262-015-1790-5 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11029563</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3972562811</sourcerecordid><originalsourceid>FETCH-LOGICAL-c531t-a8b93b14226370a590bececc124ffebf34f3039f9b17ee1595618351177853be3</originalsourceid><addsrcrecordid>eNp1kstu1TAQhi0EoqeFB2CDLLFh0YAvcRyvEKq4SZXYlLVlJ5MTlxw72E6lvCMPhc-lVUFi5ZHnm38u-hF6Rck7Soh8nwhhDasIFRWVilTiCdrQmpefVtCnaEN4TSpJSH2GzlO6LQEjSj1HZ6yRbdPKeoN-34yAne-XLrvgcRjwuOyMx7sVpuB63EN0d9DjtMxzhJRCxB1MU8J5jGHZjniE2WTX4ZTLt8lwSruE-5Cg6mEG34PP01rajM66XNTsWuoB5zWG5Dzgn86bBPdAiAl7N4XsvLOXuDfJHEJsfBkkRDPAIWGXjH3IZTbvDsAL9GwwU4KXp_cC_fj86ebqa3X9_cu3q4_XVSc4zZVpreKW1ow1XBIjFLHQQddRVg8D2IHXAydcDcpSCUCFEg1tuaBUylZwC_wCfTjqzovdQd-V9aKZ9BzdzsRVB-P03xnvRr0Nd5pSwooaLwpvTwox_FogZb1zaX854yEsSZdWTSNoo2hB3_yD3oYl-rLfniKtZI0ihaJHqisnTRGGh2ko0Xuz6KNZdDGL3ptFi1Lz-vEaDxX37igAOwKppPwW4qPW_1X9A3lr0G0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1770872690</pqid></control><display><type>article</type><title>The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>PubMed Central</source><creator>Heine, Annkristin ; Schilling, Judith ; Grünwald, Barbara ; Krüger, Achim ; Gevensleben, Heidrun ; Held, Stefanie Andrea Erika ; Garbi, Natalio ; Kurts, Christian ; Brossart, Peter ; Knolle, Percy ; Diehl, Linda ; Höchst, Bastian</creator><creatorcontrib>Heine, Annkristin ; Schilling, Judith ; Grünwald, Barbara ; Krüger, Achim ; Gevensleben, Heidrun ; Held, Stefanie Andrea Erika ; Garbi, Natalio ; Kurts, Christian ; Brossart, Peter ; Knolle, Percy ; Diehl, Linda ; Höchst, Bastian</creatorcontrib><description>Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant cell clone itself but also affect immune cells. Here, we investigate the effect of TKIs on the induction of MDSCs that differentiate from mature human monocytes using a new in vitro model of MDSC induction through activated hepatic stellate cells (HSCs). We show that frequencies of monocytic CD14
+
HLA-DR
−/low
MDSCs derived from mature monocytes were significantly and dose-dependently reduced in the presence of dasatinib, nilotinib and sorafenib, whereas sunitinib had no effect. These regulatory effects were only observed when TKIs were present during the early induction phase of MDSCs through activated HSCs, whereas already differentiated MDSCs were not further influenced by TKIs. Neither the MAPK nor the NFκB pathway was modulated in MDSCs when any of the TKIs was applied. When functional analyses were performed, we found that myeloid cells treated with sorafenib, nilotinib or dasatinib, but not sunitinib, displayed decreased suppressive capacity with regard to CD8
+
T cell proliferation. Our results indicate that sorafenib, nilotinib and dasatinib, but not sunitinib, decrease the HSC-mediated differentiation of monocytes into functional MDSCs. Therefore, treatment of cancer patients with these TKIs may in addition to having a direct effect on cancer cells also prevent the differentiation of monocytes into MDSCs and thereby differentially modulate the success of immunotherapeutic or other anti-cancer approaches.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-015-1790-5</identifier><identifier>PMID: 26786874</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cancer ; Cancer Research ; Celecoxib - pharmacology ; Cell Differentiation - drug effects ; Cells, Cultured ; Dasatinib - pharmacology ; Dose-Response Relationship, Drug ; Hematology ; Hepatic Stellate Cells - physiology ; Humans ; Immune system ; Immune Tolerance ; Immunology ; Immunotherapy ; Indoles - pharmacology ; Leukemia ; Medical prognosis ; Medicine ; Medicine & Public Health ; Monocytes - physiology ; Myeloid Cells - drug effects ; Myeloid Cells - immunology ; Niacinamide - analogs & derivatives ; Niacinamide - pharmacology ; Oncology ; Original ; Original Article ; Phenylurea Compounds - pharmacology ; Protein Kinase Inhibitors - pharmacology ; Pyrimidines - pharmacology ; Pyrroles - pharmacology ; Sorafenib ; Sunitinib</subject><ispartof>Cancer Immunology, Immunotherapy, 2016-03, Vol.65 (3), p.273-282</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-a8b93b14226370a590bececc124ffebf34f3039f9b17ee1595618351177853be3</citedby><cites>FETCH-LOGICAL-c531t-a8b93b14226370a590bececc124ffebf34f3039f9b17ee1595618351177853be3</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/PMC11029563/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11029563/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26786874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heine, Annkristin</creatorcontrib><creatorcontrib>Schilling, Judith</creatorcontrib><creatorcontrib>Grünwald, Barbara</creatorcontrib><creatorcontrib>Krüger, Achim</creatorcontrib><creatorcontrib>Gevensleben, Heidrun</creatorcontrib><creatorcontrib>Held, Stefanie Andrea Erika</creatorcontrib><creatorcontrib>Garbi, Natalio</creatorcontrib><creatorcontrib>Kurts, Christian</creatorcontrib><creatorcontrib>Brossart, Peter</creatorcontrib><creatorcontrib>Knolle, Percy</creatorcontrib><creatorcontrib>Diehl, Linda</creatorcontrib><creatorcontrib>Höchst, Bastian</creatorcontrib><title>The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant cell clone itself but also affect immune cells. Here, we investigate the effect of TKIs on the induction of MDSCs that differentiate from mature human monocytes using a new in vitro model of MDSC induction through activated hepatic stellate cells (HSCs). We show that frequencies of monocytic CD14
+
HLA-DR
−/low
MDSCs derived from mature monocytes were significantly and dose-dependently reduced in the presence of dasatinib, nilotinib and sorafenib, whereas sunitinib had no effect. These regulatory effects were only observed when TKIs were present during the early induction phase of MDSCs through activated HSCs, whereas already differentiated MDSCs were not further influenced by TKIs. Neither the MAPK nor the NFκB pathway was modulated in MDSCs when any of the TKIs was applied. When functional analyses were performed, we found that myeloid cells treated with sorafenib, nilotinib or dasatinib, but not sunitinib, displayed decreased suppressive capacity with regard to CD8
+
T cell proliferation. Our results indicate that sorafenib, nilotinib and dasatinib, but not sunitinib, decrease the HSC-mediated differentiation of monocytes into functional MDSCs. Therefore, treatment of cancer patients with these TKIs may in addition to having a direct effect on cancer cells also prevent the differentiation of monocytes into MDSCs and thereby differentially modulate the success of immunotherapeutic or other anti-cancer approaches.</description><subject>Cancer</subject><subject>Cancer Research</subject><subject>Celecoxib - pharmacology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Dasatinib - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hematology</subject><subject>Hepatic Stellate Cells - physiology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immune Tolerance</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Indoles - pharmacology</subject><subject>Leukemia</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Monocytes - physiology</subject><subject>Myeloid Cells - drug effects</subject><subject>Myeloid Cells - immunology</subject><subject>Niacinamide - analogs & derivatives</subject><subject>Niacinamide - pharmacology</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Phenylurea Compounds - pharmacology</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Pyrroles - pharmacology</subject><subject>Sorafenib</subject><subject>Sunitinib</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kstu1TAQhi0EoqeFB2CDLLFh0YAvcRyvEKq4SZXYlLVlJ5MTlxw72E6lvCMPhc-lVUFi5ZHnm38u-hF6Rck7Soh8nwhhDasIFRWVilTiCdrQmpefVtCnaEN4TSpJSH2GzlO6LQEjSj1HZ6yRbdPKeoN-34yAne-XLrvgcRjwuOyMx7sVpuB63EN0d9DjtMxzhJRCxB1MU8J5jGHZjniE2WTX4ZTLt8lwSruE-5Cg6mEG34PP01rajM66XNTsWuoB5zWG5Dzgn86bBPdAiAl7N4XsvLOXuDfJHEJsfBkkRDPAIWGXjH3IZTbvDsAL9GwwU4KXp_cC_fj86ebqa3X9_cu3q4_XVSc4zZVpreKW1ow1XBIjFLHQQddRVg8D2IHXAydcDcpSCUCFEg1tuaBUylZwC_wCfTjqzovdQd-V9aKZ9BzdzsRVB-P03xnvRr0Nd5pSwooaLwpvTwox_FogZb1zaX854yEsSZdWTSNoo2hB3_yD3oYl-rLfniKtZI0ihaJHqisnTRGGh2ko0Xuz6KNZdDGL3ptFi1Lz-vEaDxX37igAOwKppPwW4qPW_1X9A3lr0G0</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Heine, Annkristin</creator><creator>Schilling, Judith</creator><creator>Grünwald, Barbara</creator><creator>Krüger, Achim</creator><creator>Gevensleben, Heidrun</creator><creator>Held, Stefanie Andrea Erika</creator><creator>Garbi, Natalio</creator><creator>Kurts, Christian</creator><creator>Brossart, Peter</creator><creator>Knolle, Percy</creator><creator>Diehl, Linda</creator><creator>Höchst, Bastian</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20160301</creationdate><title>The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib</title><author>Heine, Annkristin ; Schilling, Judith ; Grünwald, Barbara ; Krüger, Achim ; Gevensleben, Heidrun ; Held, Stefanie Andrea Erika ; Garbi, Natalio ; Kurts, Christian ; Brossart, Peter ; Knolle, Percy ; Diehl, Linda ; Höchst, Bastian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c531t-a8b93b14226370a590bececc124ffebf34f3039f9b17ee1595618351177853be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cancer</topic><topic>Cancer Research</topic><topic>Celecoxib - pharmacology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Dasatinib - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hematology</topic><topic>Hepatic Stellate Cells - physiology</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immune Tolerance</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Indoles - pharmacology</topic><topic>Leukemia</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Monocytes - physiology</topic><topic>Myeloid Cells - drug effects</topic><topic>Myeloid Cells - immunology</topic><topic>Niacinamide - analogs & derivatives</topic><topic>Niacinamide - pharmacology</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Phenylurea Compounds - pharmacology</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Pyrimidines - pharmacology</topic><topic>Pyrroles - pharmacology</topic><topic>Sorafenib</topic><topic>Sunitinib</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heine, Annkristin</creatorcontrib><creatorcontrib>Schilling, Judith</creatorcontrib><creatorcontrib>Grünwald, Barbara</creatorcontrib><creatorcontrib>Krüger, Achim</creatorcontrib><creatorcontrib>Gevensleben, Heidrun</creatorcontrib><creatorcontrib>Held, Stefanie Andrea Erika</creatorcontrib><creatorcontrib>Garbi, Natalio</creatorcontrib><creatorcontrib>Kurts, Christian</creatorcontrib><creatorcontrib>Brossart, Peter</creatorcontrib><creatorcontrib>Knolle, Percy</creatorcontrib><creatorcontrib>Diehl, Linda</creatorcontrib><creatorcontrib>Höchst, Bastian</creatorcontrib><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 Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</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>Heine, Annkristin</au><au>Schilling, Judith</au><au>Grünwald, Barbara</au><au>Krüger, Achim</au><au>Gevensleben, Heidrun</au><au>Held, Stefanie Andrea Erika</au><au>Garbi, Natalio</au><au>Kurts, Christian</au><au>Brossart, Peter</au><au>Knolle, Percy</au><au>Diehl, Linda</au><au>Höchst, Bastian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>65</volume><issue>3</issue><spage>273</spage><epage>282</epage><pages>273-282</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant cell clone itself but also affect immune cells. Here, we investigate the effect of TKIs on the induction of MDSCs that differentiate from mature human monocytes using a new in vitro model of MDSC induction through activated hepatic stellate cells (HSCs). We show that frequencies of monocytic CD14
+
HLA-DR
−/low
MDSCs derived from mature monocytes were significantly and dose-dependently reduced in the presence of dasatinib, nilotinib and sorafenib, whereas sunitinib had no effect. These regulatory effects were only observed when TKIs were present during the early induction phase of MDSCs through activated HSCs, whereas already differentiated MDSCs were not further influenced by TKIs. Neither the MAPK nor the NFκB pathway was modulated in MDSCs when any of the TKIs was applied. When functional analyses were performed, we found that myeloid cells treated with sorafenib, nilotinib or dasatinib, but not sunitinib, displayed decreased suppressive capacity with regard to CD8
+
T cell proliferation. Our results indicate that sorafenib, nilotinib and dasatinib, but not sunitinib, decrease the HSC-mediated differentiation of monocytes into functional MDSCs. Therefore, treatment of cancer patients with these TKIs may in addition to having a direct effect on cancer cells also prevent the differentiation of monocytes into MDSCs and thereby differentially modulate the success of immunotherapeutic or other anti-cancer approaches.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26786874</pmid><doi>10.1007/s00262-015-1790-5</doi><tpages>10</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0340-7004 |
ispartof | Cancer Immunology, Immunotherapy, 2016-03, Vol.65 (3), p.273-282 |
issn | 0340-7004 1432-0851 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11029563 |
source | MEDLINE; Springer Nature - Complete Springer Journals; PubMed Central |
subjects | Cancer Cancer Research Celecoxib - pharmacology Cell Differentiation - drug effects Cells, Cultured Dasatinib - pharmacology Dose-Response Relationship, Drug Hematology Hepatic Stellate Cells - physiology Humans Immune system Immune Tolerance Immunology Immunotherapy Indoles - pharmacology Leukemia Medical prognosis Medicine Medicine & Public Health Monocytes - physiology Myeloid Cells - drug effects Myeloid Cells - immunology Niacinamide - analogs & derivatives Niacinamide - pharmacology Oncology Original Original Article Phenylurea Compounds - pharmacology Protein Kinase Inhibitors - pharmacology Pyrimidines - pharmacology Pyrroles - pharmacology Sorafenib Sunitinib |
title | The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T22%3A48%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20induction%20of%20human%20myeloid%20derived%20suppressor%20cells%20through%20hepatic%20stellate%20cells%20is%20dose-dependently%20inhibited%20by%20the%20tyrosine%20kinase%20inhibitors%20nilotinib,%20dasatinib%20and%20sorafenib,%20but%20not%20sunitinib&rft.jtitle=Cancer%20Immunology,%20Immunotherapy&rft.au=Heine,%20Annkristin&rft.date=2016-03-01&rft.volume=65&rft.issue=3&rft.spage=273&rft.epage=282&rft.pages=273-282&rft.issn=0340-7004&rft.eissn=1432-0851&rft_id=info:doi/10.1007/s00262-015-1790-5&rft_dat=%3Cproquest_pubme%3E3972562811%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1770872690&rft_id=info:pmid/26786874&rfr_iscdi=true |