MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti‐PD‐1 immunotherapy in patients with advanced NSCLC
The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T‐cell activities and supporting tumor progression and survival. In this study,...
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| Veröffentlicht in: | European journal of immunology 2020-11, Vol.50 (11), p.1810-1819 |
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| creator | Koh, Jiae Kim, Youjin Lee, Kyoung Young Hur, Joon Young Kim, Mi Soon Kim, Boram Cho, Hee Jin Lee, Yeong Chan Bae, Yeon Hee Ku, Bo Mi Sun, Jong‐Mu Lee, Se‐Hoon Ahn, Jin Seok Park, Keunchil Ahn, Myung‐Ju |
| description | The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T‐cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non‐small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T‐cell activities leading to poor clinical outcomes. First, we verified PMN‐MDSCs, monocytic‐MDSCs (M‐MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T‐cell activities and induced T‐cell exhaustion. The analysis of NSCLC patients treated with anti‐PD‐1 immunotherapy demonstrated that low PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.
Pre‐existing PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells can be used as predictive biomarkers in anti‐PD‐1 immunotherapy targeting NSCLC. Together with MDSCs, IL‐10 possibly released by suppressive immune cells also leads poor clinical outcomes. Therefore, combinatorial strategies targeting MDSCs or IL‐10 should be investigated to improve outcomes of immune checkpoint inhibitors. |
| doi_str_mv | 10.1002/eji.202048534 |
| format | Article |
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Pre‐existing PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells can be used as predictive biomarkers in anti‐PD‐1 immunotherapy targeting NSCLC. Together with MDSCs, IL‐10 possibly released by suppressive immune cells also leads poor clinical outcomes. Therefore, combinatorial strategies targeting MDSCs or IL‐10 should be investigated to improve outcomes of immune checkpoint inhibitors.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.202048534</identifier><identifier>PMID: 32510574</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antigens, CD - immunology ; Apyrase - immunology ; Carcinoma, Non-Small-Cell Lung - immunology ; CD39 ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Clinical ; Female ; Humans ; IL‐10 ; Immune checkpoint inhibitor ; Immunotherapy ; Immunotherapy - methods ; Lung cancer ; Lung Neoplasms - immunology ; Lymphocyte Activation - immunology ; Lymphocytes ; Lymphocytes T ; Macrophages ; Male ; MDSC ; Middle Aged ; Monocytes ; Myeloid-Derived Suppressor Cells - immunology ; Non-small cell lung carcinoma ; Non‐small cell lung cancer ; Peripheral blood ; Programmed Cell Death 1 Receptor - immunology ; Small cell lung carcinoma ; Suppressor cells ; Tumor immunology</subject><ispartof>European journal of immunology, 2020-11, Vol.50 (11), p.1810-1819</ispartof><rights>2020 The Authors. published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4250-3cf9f5f298b586379981660ad21e90e5f614e3a9776a2d55051312476e0b52fb3</citedby><cites>FETCH-LOGICAL-c4250-3cf9f5f298b586379981660ad21e90e5f614e3a9776a2d55051312476e0b52fb3</cites><orcidid>0000-0003-2309-0697</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Feji.202048534$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.202048534$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32510574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koh, Jiae</creatorcontrib><creatorcontrib>Kim, Youjin</creatorcontrib><creatorcontrib>Lee, Kyoung Young</creatorcontrib><creatorcontrib>Hur, Joon Young</creatorcontrib><creatorcontrib>Kim, Mi Soon</creatorcontrib><creatorcontrib>Kim, Boram</creatorcontrib><creatorcontrib>Cho, Hee Jin</creatorcontrib><creatorcontrib>Lee, Yeong Chan</creatorcontrib><creatorcontrib>Bae, Yeon Hee</creatorcontrib><creatorcontrib>Ku, Bo Mi</creatorcontrib><creatorcontrib>Sun, Jong‐Mu</creatorcontrib><creatorcontrib>Lee, Se‐Hoon</creatorcontrib><creatorcontrib>Ahn, Jin Seok</creatorcontrib><creatorcontrib>Park, Keunchil</creatorcontrib><creatorcontrib>Ahn, Myung‐Ju</creatorcontrib><title>MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti‐PD‐1 immunotherapy in patients with advanced NSCLC</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T‐cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non‐small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T‐cell activities leading to poor clinical outcomes. First, we verified PMN‐MDSCs, monocytic‐MDSCs (M‐MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T‐cell activities and induced T‐cell exhaustion. The analysis of NSCLC patients treated with anti‐PD‐1 immunotherapy demonstrated that low PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.
Pre‐existing PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells can be used as predictive biomarkers in anti‐PD‐1 immunotherapy targeting NSCLC. Together with MDSCs, IL‐10 possibly released by suppressive immune cells also leads poor clinical outcomes. Therefore, combinatorial strategies targeting MDSCs or IL‐10 should be investigated to improve outcomes of immune checkpoint inhibitors.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, CD - immunology</subject><subject>Apyrase - immunology</subject><subject>Carcinoma, Non-Small-Cell Lung - immunology</subject><subject>CD39</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Clinical</subject><subject>Female</subject><subject>Humans</subject><subject>IL‐10</subject><subject>Immune checkpoint inhibitor</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - immunology</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Male</subject><subject>MDSC</subject><subject>Middle Aged</subject><subject>Monocytes</subject><subject>Myeloid-Derived Suppressor Cells - immunology</subject><subject>Non-small cell lung carcinoma</subject><subject>Non‐small cell lung cancer</subject><subject>Peripheral blood</subject><subject>Programmed Cell Death 1 Receptor - immunology</subject><subject>Small cell lung carcinoma</subject><subject>Suppressor cells</subject><subject>Tumor immunology</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAUhS0EotOBJVtkiSVKuX4m3iChTAuthofUsrYcx2Y8yiQhTtpm1w17fiO_BFdTRrBBsuwr3c_nnquD0AsCJwSAvnHbcEKBAi8E44_QgghKMk44eYwWAIRnVBVwhI5j3AKAkkI9RUeMCgIi5wv04-PqssRxqsa5dxGbtsbliinsbvvBxRi6FqdTrorX-Apb1zQRp0Yd7IjHjcPO-2CNnXHn098x_Lr7-WWVLoLDbje1XWIG0884tLg3Y3DtGPFNGDfY1Nemta7Gny7LdfkMPfGmie75w7tEX89Or8oP2frz-_Py3TqznArImPXKC582qkQhWa5UQaQEU1PiFDjhJeGOGZXn0tBaCBCEEcpz6aAS1Fdsid7udfup2rnaJj-DaXQ_hJ0ZZt2ZoP_ttGGjv3XXOpeFkmnkEr16EBi675OLo95209Amz5pykRcFpQVJVLan7NDFODh_mEBA36emU2r6kFriX_5t60D_iSkBdA_chMbN_1fTpxfnqQD2G--iotM</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Koh, Jiae</creator><creator>Kim, Youjin</creator><creator>Lee, Kyoung Young</creator><creator>Hur, Joon Young</creator><creator>Kim, Mi Soon</creator><creator>Kim, Boram</creator><creator>Cho, Hee Jin</creator><creator>Lee, Yeong Chan</creator><creator>Bae, Yeon Hee</creator><creator>Ku, Bo Mi</creator><creator>Sun, Jong‐Mu</creator><creator>Lee, Se‐Hoon</creator><creator>Ahn, Jin Seok</creator><creator>Park, Keunchil</creator><creator>Ahn, Myung‐Ju</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2309-0697</orcidid></search><sort><creationdate>202011</creationdate><title>MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti‐PD‐1 immunotherapy in patients with advanced NSCLC</title><author>Koh, Jiae ; Kim, Youjin ; Lee, Kyoung Young ; Hur, Joon Young ; Kim, Mi Soon ; Kim, Boram ; Cho, Hee Jin ; Lee, Yeong Chan ; Bae, Yeon Hee ; Ku, Bo Mi ; Sun, Jong‐Mu ; Lee, Se‐Hoon ; Ahn, Jin Seok ; Park, Keunchil ; Ahn, Myung‐Ju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4250-3cf9f5f298b586379981660ad21e90e5f614e3a9776a2d55051312476e0b52fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens, CD - immunology</topic><topic>Apyrase - immunology</topic><topic>Carcinoma, Non-Small-Cell Lung - immunology</topic><topic>CD39</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Clinical</topic><topic>Female</topic><topic>Humans</topic><topic>IL‐10</topic><topic>Immune checkpoint inhibitor</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - immunology</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Male</topic><topic>MDSC</topic><topic>Middle Aged</topic><topic>Monocytes</topic><topic>Myeloid-Derived Suppressor Cells - immunology</topic><topic>Non-small cell lung carcinoma</topic><topic>Non‐small cell lung cancer</topic><topic>Peripheral blood</topic><topic>Programmed Cell Death 1 Receptor - immunology</topic><topic>Small cell lung carcinoma</topic><topic>Suppressor cells</topic><topic>Tumor immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koh, Jiae</creatorcontrib><creatorcontrib>Kim, Youjin</creatorcontrib><creatorcontrib>Lee, Kyoung Young</creatorcontrib><creatorcontrib>Hur, Joon Young</creatorcontrib><creatorcontrib>Kim, Mi Soon</creatorcontrib><creatorcontrib>Kim, Boram</creatorcontrib><creatorcontrib>Cho, Hee Jin</creatorcontrib><creatorcontrib>Lee, Yeong Chan</creatorcontrib><creatorcontrib>Bae, Yeon Hee</creatorcontrib><creatorcontrib>Ku, Bo Mi</creatorcontrib><creatorcontrib>Sun, Jong‐Mu</creatorcontrib><creatorcontrib>Lee, Se‐Hoon</creatorcontrib><creatorcontrib>Ahn, Jin Seok</creatorcontrib><creatorcontrib>Park, Keunchil</creatorcontrib><creatorcontrib>Ahn, Myung‐Ju</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koh, Jiae</au><au>Kim, Youjin</au><au>Lee, Kyoung Young</au><au>Hur, Joon Young</au><au>Kim, Mi Soon</au><au>Kim, Boram</au><au>Cho, Hee Jin</au><au>Lee, Yeong Chan</au><au>Bae, Yeon Hee</au><au>Ku, Bo Mi</au><au>Sun, Jong‐Mu</au><au>Lee, Se‐Hoon</au><au>Ahn, Jin Seok</au><au>Park, Keunchil</au><au>Ahn, Myung‐Ju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti‐PD‐1 immunotherapy in patients with advanced NSCLC</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2020-11</date><risdate>2020</risdate><volume>50</volume><issue>11</issue><spage>1810</spage><epage>1819</epage><pages>1810-1819</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T‐cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non‐small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T‐cell activities leading to poor clinical outcomes. First, we verified PMN‐MDSCs, monocytic‐MDSCs (M‐MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T‐cell activities and induced T‐cell exhaustion. The analysis of NSCLC patients treated with anti‐PD‐1 immunotherapy demonstrated that low PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.
Pre‐existing PMN‐MDSCs, M‐MDSCs, and CD39+CD8+ T cells can be used as predictive biomarkers in anti‐PD‐1 immunotherapy targeting NSCLC. Together with MDSCs, IL‐10 possibly released by suppressive immune cells also leads poor clinical outcomes. Therefore, combinatorial strategies targeting MDSCs or IL‐10 should be investigated to improve outcomes of immune checkpoint inhibitors.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32510574</pmid><doi>10.1002/eji.202048534</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2309-0697</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antigens, CD - immunology Apyrase - immunology Carcinoma, Non-Small-Cell Lung - immunology CD39 CD8 antigen CD8-Positive T-Lymphocytes - immunology Clinical Female Humans IL‐10 Immune checkpoint inhibitor Immunotherapy Immunotherapy - methods Lung cancer Lung Neoplasms - immunology Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Macrophages Male MDSC Middle Aged Monocytes Myeloid-Derived Suppressor Cells - immunology Non-small cell lung carcinoma Non‐small cell lung cancer Peripheral blood Programmed Cell Death 1 Receptor - immunology Small cell lung carcinoma Suppressor cells Tumor immunology |
| title | MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti‐PD‐1 immunotherapy in patients with advanced NSCLC |
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