Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non‐small cell lung cancer
The evaluation of PD‐L1 expression alone has limitations in predicting clinical outcome in immune‐checkpoint inhibitors (ICI). This study aimed to evaluate the predictive and prognostic effects of the presence of various immune cells in pretreatment tissue samples and to identify determinants associ...
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| Veröffentlicht in: | European journal of immunology 2021-04, Vol.51 (4), p.956-964 |
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| container_title | European journal of immunology |
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| creator | Ku, Bo Mi Kim, Youjin Lee, Kyoung Young Kim, Sang‐Yeob Sun, Jong‐Mu Lee, Se‐Hoon Ahn, Jin Seok Park, Keunchil Ahn, Myung‐Ju |
| description | The evaluation of PD‐L1 expression alone has limitations in predicting clinical outcome in immune‐checkpoint inhibitors (ICI). This study aimed to evaluate the predictive and prognostic effects of the presence of various immune cells in pretreatment tissue samples and to identify determinants associated with response in patients with advanced non‐small cell lung cancer (NSCLC) treated with PD‐1 blockade. Immune cell distribution was heterogeneous and the most dominant immune cell type was T cells. Patients with durable clinical benefit (DCB) showed significantly higher PD‐L1 expression. The ratio of tumor/stroma region of T cell, B cell, and macrophage was significantly higher in patient with DCB. High intratumoral T‐ and B‐cell density (≥median) was associated with DCB in the low PD‐L1 expression ( |
| doi_str_mv | 10.1002/eji.202048966 |
| format | Article |
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Pre‐existing immune cells in tumor microenvironment represent key factors in determining clinical response to immunotherapy. High T‐ and B‐cell density has prognostic and predictive potential in combination with PD‐L1. In addition, immune cell proportions are related with risk of hyperprogressive disease.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.202048966</identifier><identifier>PMID: 33506525</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Cell density ; Clinical ; Durable clinical benefit ; Hyperprogressive disease ; Immune checkpoint inhibitor ; Immune checkpoint inhibitors ; Lung cancer ; Lymphocytes T ; Macrophages ; Non-small cell lung carcinoma ; Non‐small cell lung cancer ; PD-L1 protein ; Small cell lung carcinoma ; Stroma ; Tumor immunology ; Tumor microenvironment</subject><ispartof>European journal of immunology, 2021-04, Vol.51 (4), p.956-964</ispartof><rights>2021 The Authors. published by Wiley‐VCH GmbH</rights><rights>2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.</rights><rights>2021. 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-c4589-2be42af94df92c0029885a5538ff5a56f4d9a03533f52ba4dbb4462eede4842f3</citedby><cites>FETCH-LOGICAL-c4589-2be42af94df92c0029885a5538ff5a56f4d9a03533f52ba4dbb4462eede4842f3</cites><orcidid>0000-0002-5740-9654</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.202048966$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.202048966$$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/33506525$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ku, Bo Mi</creatorcontrib><creatorcontrib>Kim, Youjin</creatorcontrib><creatorcontrib>Lee, Kyoung Young</creatorcontrib><creatorcontrib>Kim, Sang‐Yeob</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>Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non‐small cell lung cancer</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>The evaluation of PD‐L1 expression alone has limitations in predicting clinical outcome in immune‐checkpoint inhibitors (ICI). This study aimed to evaluate the predictive and prognostic effects of the presence of various immune cells in pretreatment tissue samples and to identify determinants associated with response in patients with advanced non‐small cell lung cancer (NSCLC) treated with PD‐1 blockade. Immune cell distribution was heterogeneous and the most dominant immune cell type was T cells. Patients with durable clinical benefit (DCB) showed significantly higher PD‐L1 expression. The ratio of tumor/stroma region of T cell, B cell, and macrophage was significantly higher in patient with DCB. High intratumoral T‐ and B‐cell density (≥median) was associated with DCB in the low PD‐L1 expression (<50%) group. In univariate analyses, the overall survival (OS) benefit was shown according to intratumoral B‐cell density (p = 0.0337). The incidence of hyperprogressive disease (HPD) was 13.0%. The Chi‐square test revealed that HPD was significantly associated with intratumoral B‐cell density but not T‐cell or macrophage density. Our results demonstrate different predictive and prognostic values for infiltrating immune cells in tumor tissue, which may help in selecting patients for ICI.
Pre‐existing immune cells in tumor microenvironment represent key factors in determining clinical response to immunotherapy. High T‐ and B‐cell density has prognostic and predictive potential in combination with PD‐L1. In addition, immune cell proportions are related with risk of hyperprogressive disease.</description><subject>Cell density</subject><subject>Clinical</subject><subject>Durable clinical benefit</subject><subject>Hyperprogressive disease</subject><subject>Immune checkpoint inhibitor</subject><subject>Immune checkpoint inhibitors</subject><subject>Lung cancer</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Non-small cell lung carcinoma</subject><subject>Non‐small cell lung cancer</subject><subject>PD-L1 protein</subject><subject>Small cell lung carcinoma</subject><subject>Stroma</subject><subject>Tumor immunology</subject><subject>Tumor microenvironment</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp9kb1uFDEUhS0EIkugpEWWaGgm-HdkN0goCiQoEk2oLY_HznqZsQf_JNouj5Bn5EniZcMKKKiu5Pv53HvuAeA1RicYIfLebvwJQQQxIfv-CVhhTnDHMMNPwQohzDoiBToCL3LeIIRkz-VzcEQpRz0nfAXur-ocE_TB-akkXewI_TzXYKGx0wTLdrEZ5rosMRU4-lx8MOWArK35vkQf2ktY-8GXJhVrMXFuv3yAiy7ehpLhrS9rqMcbHUybEGL4eXefZ90m_Boz1XANza6ZXoJnTk_Zvnqsx-Dbp7Or0_Pu8uvni9OPl51hXMiODJYR7SQbnSSmHUIKwTXnVDjXau_YKDWinFLHyaDZOAyM9cTa0TLBiKPH4MNed6nDbEfT1kx6Ukvys05bFbVXf3eCX6vreKMEYYJQ0QTePQqk-KPaXNTs886NDjbWrHZY3wspeUPf_oNuYk2h2VOEY4oEYoQ2qttTJsWck3WHZTBSu6xVy1odsm78mz8dHOjf4TaA7IFbP9nt_9XU2ZcLJoWkDzP3uZQ</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Ku, Bo Mi</creator><creator>Kim, Youjin</creator><creator>Lee, Kyoung Young</creator><creator>Kim, Sang‐Yeob</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>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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5740-9654</orcidid></search><sort><creationdate>202104</creationdate><title>Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non‐small cell lung cancer</title><author>Ku, Bo Mi ; Kim, Youjin ; Lee, Kyoung Young ; Kim, Sang‐Yeob ; Sun, Jong‐Mu ; Lee, Se‐Hoon ; Ahn, Jin Seok ; Park, Keunchil ; Ahn, Myung‐Ju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4589-2be42af94df92c0029885a5538ff5a56f4d9a03533f52ba4dbb4462eede4842f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cell density</topic><topic>Clinical</topic><topic>Durable clinical benefit</topic><topic>Hyperprogressive disease</topic><topic>Immune checkpoint inhibitor</topic><topic>Immune checkpoint inhibitors</topic><topic>Lung cancer</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Non-small cell lung carcinoma</topic><topic>Non‐small cell lung cancer</topic><topic>PD-L1 protein</topic><topic>Small cell lung carcinoma</topic><topic>Stroma</topic><topic>Tumor immunology</topic><topic>Tumor microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ku, Bo Mi</creatorcontrib><creatorcontrib>Kim, Youjin</creatorcontrib><creatorcontrib>Lee, Kyoung Young</creatorcontrib><creatorcontrib>Kim, Sang‐Yeob</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 Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</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>MEDLINE - Academic</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>Ku, Bo Mi</au><au>Kim, Youjin</au><au>Lee, Kyoung Young</au><au>Kim, Sang‐Yeob</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>Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non‐small cell lung cancer</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2021-04</date><risdate>2021</risdate><volume>51</volume><issue>4</issue><spage>956</spage><epage>964</epage><pages>956-964</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>The evaluation of PD‐L1 expression alone has limitations in predicting clinical outcome in immune‐checkpoint inhibitors (ICI). This study aimed to evaluate the predictive and prognostic effects of the presence of various immune cells in pretreatment tissue samples and to identify determinants associated with response in patients with advanced non‐small cell lung cancer (NSCLC) treated with PD‐1 blockade. Immune cell distribution was heterogeneous and the most dominant immune cell type was T cells. Patients with durable clinical benefit (DCB) showed significantly higher PD‐L1 expression. The ratio of tumor/stroma region of T cell, B cell, and macrophage was significantly higher in patient with DCB. High intratumoral T‐ and B‐cell density (≥median) was associated with DCB in the low PD‐L1 expression (<50%) group. In univariate analyses, the overall survival (OS) benefit was shown according to intratumoral B‐cell density (p = 0.0337). The incidence of hyperprogressive disease (HPD) was 13.0%. The Chi‐square test revealed that HPD was significantly associated with intratumoral B‐cell density but not T‐cell or macrophage density. Our results demonstrate different predictive and prognostic values for infiltrating immune cells in tumor tissue, which may help in selecting patients for ICI.
Pre‐existing immune cells in tumor microenvironment represent key factors in determining clinical response to immunotherapy. High T‐ and B‐cell density has prognostic and predictive potential in combination with PD‐L1. In addition, immune cell proportions are related with risk of hyperprogressive disease.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33506525</pmid><doi>10.1002/eji.202048966</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5740-9654</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cell density Clinical Durable clinical benefit Hyperprogressive disease Immune checkpoint inhibitor Immune checkpoint inhibitors Lung cancer Lymphocytes T Macrophages Non-small cell lung carcinoma Non‐small cell lung cancer PD-L1 protein Small cell lung carcinoma Stroma Tumor immunology Tumor microenvironment |
| title | Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non‐small cell lung cancer |
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