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PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer
•We evaluated PD-L1 expression on tumor cells (TCs) and immune cells (ICs).•Relationship between M2 tumor-associated macrophages (TAMs) and PD-L1 was studied.•PD-L1 expression on TCs and ICs was higher in patients with M2 TAM-high tumors.•PD-L1 on ICs rather than TCs was more related to aggressive m...
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Published in: | Lung cancer (Amsterdam, Netherlands) Netherlands), 2019-10, Vol.136, p.136-144 |
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creator | Sumitomo, Ryota Hirai, Tatsuya Fujita, Masaaki Murakami, Hiroaki Otake, Yosuke Huang, Cheng-long |
description | •We evaluated PD-L1 expression on tumor cells (TCs) and immune cells (ICs).•Relationship between M2 tumor-associated macrophages (TAMs) and PD-L1 was studied.•PD-L1 expression on TCs and ICs was higher in patients with M2 TAM-high tumors.•PD-L1 on ICs rather than TCs was more related to aggressive malignant behaviors.•The presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs in NSCLC.
PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression.
We evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC).
PD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p |
doi_str_mv | 10.1016/j.lungcan.2019.08.023 |
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PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression.
We evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC).
PD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023).
During tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.]]></description><identifier>ISSN: 0169-5002</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2019.08.023</identifier><identifier>PMID: 31499335</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>CD163 ; Immune cells ; Macrophage ; PD-L1 ; Prognosis</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2019-10, Vol.136, p.136-144</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-e716a94de00c35c4a292bbe60d4c8ccb6a0a9a9c7016ade66a2fc6e49eede6763</citedby><cites>FETCH-LOGICAL-c365t-e716a94de00c35c4a292bbe60d4c8ccb6a0a9a9c7016ade66a2fc6e49eede6763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31499335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sumitomo, Ryota</creatorcontrib><creatorcontrib>Hirai, Tatsuya</creatorcontrib><creatorcontrib>Fujita, Masaaki</creatorcontrib><creatorcontrib>Murakami, Hiroaki</creatorcontrib><creatorcontrib>Otake, Yosuke</creatorcontrib><creatorcontrib>Huang, Cheng-long</creatorcontrib><title>PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description><![CDATA[•We evaluated PD-L1 expression on tumor cells (TCs) and immune cells (ICs).•Relationship between M2 tumor-associated macrophages (TAMs) and PD-L1 was studied.•PD-L1 expression on TCs and ICs was higher in patients with M2 TAM-high tumors.•PD-L1 on ICs rather than TCs was more related to aggressive malignant behaviors.•The presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs in NSCLC.
PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression.
We evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC).
PD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023).
During tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.]]></description><subject>CD163</subject><subject>Immune cells</subject><subject>Macrophage</subject><subject>PD-L1</subject><subject>Prognosis</subject><issn>0169-5002</issn><issn>1872-8332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFUU1v1DAUtBCILoWfAPKRS4LtJE58QlXLl7QVHMrZeuu8zXqV2MF2Cv1P_Eic7sIVyZL1pJl5b2YIec1ZyRmX747luLjBgCsF46pkXclE9YRseNeKoqsq8ZRsMk4VDWPigryI8cgYbzlTz8lFxWulqqrZkN_fbootp_hrDhij9Y7ml5bJh8K6vR1TgGTdQO00LQ6pwXGM1EZ6sMNhfKAQozcWEvb0p00Heivo3dUtBddTGIZHyXukE4x2cOASnX1ClyyM1Do6Z-k8xRM1g9GsQs67ImbK-LiNrjZp9mkwvCTP9jBGfHX-L8n3jx_urj8X26-fvlxfbQtTySYV2HIJqu6RMVM1pgahxG6HkvW16YzZSWCgQJk25wM9SglibyTWCjFPrawuyduT7hz8jwVj0pON6zHg0C9RC9F1OcyuqTO0OUFN8DEG3Os52AnCg-ZMr0Xpoz4XpdeiNOt0Lirz3pxXLLsJ-3-sv81kwPsTALPRe4tBR5PTMtjbkHPSvbf_WfEHoaerfA</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Sumitomo, Ryota</creator><creator>Hirai, Tatsuya</creator><creator>Fujita, Masaaki</creator><creator>Murakami, Hiroaki</creator><creator>Otake, Yosuke</creator><creator>Huang, Cheng-long</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201910</creationdate><title>PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer</title><author>Sumitomo, Ryota ; Hirai, Tatsuya ; Fujita, Masaaki ; Murakami, Hiroaki ; Otake, Yosuke ; Huang, Cheng-long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-e716a94de00c35c4a292bbe60d4c8ccb6a0a9a9c7016ade66a2fc6e49eede6763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>CD163</topic><topic>Immune cells</topic><topic>Macrophage</topic><topic>PD-L1</topic><topic>Prognosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sumitomo, Ryota</creatorcontrib><creatorcontrib>Hirai, Tatsuya</creatorcontrib><creatorcontrib>Fujita, Masaaki</creatorcontrib><creatorcontrib>Murakami, Hiroaki</creatorcontrib><creatorcontrib>Otake, Yosuke</creatorcontrib><creatorcontrib>Huang, Cheng-long</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sumitomo, Ryota</au><au>Hirai, Tatsuya</au><au>Fujita, Masaaki</au><au>Murakami, Hiroaki</au><au>Otake, Yosuke</au><au>Huang, Cheng-long</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2019-10</date><risdate>2019</risdate><volume>136</volume><spage>136</spage><epage>144</epage><pages>136-144</pages><issn>0169-5002</issn><eissn>1872-8332</eissn><abstract><![CDATA[•We evaluated PD-L1 expression on tumor cells (TCs) and immune cells (ICs).•Relationship between M2 tumor-associated macrophages (TAMs) and PD-L1 was studied.•PD-L1 expression on TCs and ICs was higher in patients with M2 TAM-high tumors.•PD-L1 on ICs rather than TCs was more related to aggressive malignant behaviors.•The presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs in NSCLC.
PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression.
We evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC).
PD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023).
During tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.]]></abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31499335</pmid><doi>10.1016/j.lungcan.2019.08.023</doi><tpages>9</tpages></addata></record> |
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title | PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer |
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