Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes
Background B7 homolog 4 ( B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cel...
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| Veröffentlicht in: | Breast cancer (Tokyo, Japan) Japan), 2023-11, Vol.30 (6), p.1041-1053 |
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| container_title | Breast cancer (Tokyo, Japan) |
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| creator | Sanuki, Fumiaki Mikami, Yuka Nishimura, Hirotake Fujita, Yoshinori Monobe, Yasumasa Nomura, Tsunehisa Taira, Naruto Moriya, Takuya |
| description | Background
B7 homolog 4
(
B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes.
Methods
Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor–stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression.
Results
B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28–8;
p
= 0.021), inflamed TIL pattern (
p
= 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = − 0.509,
p
|
| doi_str_mv | 10.1007/s12282-023-01498-7 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2858990754</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A769635185</galeid><sourcerecordid>A769635185</sourcerecordid><originalsourceid>FETCH-LOGICAL-c303t-f6174eabdf798f7506cb013f8d893f0a5f72faf16c25a8c62a4f48c350cb63a93</originalsourceid><addsrcrecordid>eNp9kc9u1DAQhyMEEqXwApwsceFQg_8ksXMsLdCVVioHOFuOd7y4SuzgcSr2NXhivA1nTjOa-X4jjb6mecvZB86Y-ohcCC0oE5Iy3g6aqmfNBdea0VZI-bz2smW0171-2bxCfGCslYr1F82f3TyvMf0MWNKUjsHZidhopxMGJMmTT4retVdkd3vPr-riQL7d0j0n8HvJgBhSfBqWdU6ZhPMpIHNwOUF8DDnFGWIho0U4kIqWHJYJaISjLeERyJjBYiHORgeZ4DqW0wL4unnh7YTw5l-9bH58-fz95o7u77_ubq731EkmC_U9Vy3Y8eDVoL3qWO9GxqXXBz1Iz2znlfDW896JzmrXC9v6VjvZMTf20g7ysnm_3V1y-rUCFjMHdDBNNkJa0Qjd6WFgqmsr-m5Dj3YCE6JPJVt3xs216odedlx3lRIbVf9HzODNksNs88lwZs6azKbJVE3mSZNRNSS3EFY4HiGbh7TmagD_l_oLXHCWZg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2858990754</pqid></control><display><type>article</type><title>Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes</title><source>SpringerNature Journals</source><creator>Sanuki, Fumiaki ; Mikami, Yuka ; Nishimura, Hirotake ; Fujita, Yoshinori ; Monobe, Yasumasa ; Nomura, Tsunehisa ; Taira, Naruto ; Moriya, Takuya</creator><creatorcontrib>Sanuki, Fumiaki ; Mikami, Yuka ; Nishimura, Hirotake ; Fujita, Yoshinori ; Monobe, Yasumasa ; Nomura, Tsunehisa ; Taira, Naruto ; Moriya, Takuya</creatorcontrib><description>Background
B7 homolog 4
(
B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes.
Methods
Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor–stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression.
Results
B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28–8;
p
= 0.021), inflamed TIL pattern (
p
= 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = − 0.509,
p
< 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 (
ρ
= − 0.354,
p
< 0.001).
Conclusions
These results suggest that considering the TIL pattern and TLS and identifying the expression of PD-L1 and the basal-like type are useful for estimating B7-H4 expression. In addition, luminal androgen receptor (LAR)-type is frequently deficient in B7-H4 expression. In non-LAR types, B7-H4 and IDO1 expression are exclusive.</description><identifier>ISSN: 1340-6868</identifier><identifier>EISSN: 1880-4233</identifier><identifier>DOI: 10.1007/s12282-023-01498-7</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Analysis ; Apoptosis ; Breast cancer ; Cancer Research ; Health aspects ; Immunohistochemistry ; Keratin ; Lymphocytes ; Medicine ; Medicine & Public Health ; Oncology ; Original Article ; Surgery ; Surgical Oncology</subject><ispartof>Breast cancer (Tokyo, Japan), 2023-11, Vol.30 (6), p.1041-1053</ispartof><rights>The Author(s), under exclusive licence to The Japanese Breast Cancer Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>COPYRIGHT 2023 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c303t-f6174eabdf798f7506cb013f8d893f0a5f72faf16c25a8c62a4f48c350cb63a93</cites><orcidid>0000-0002-7357-3243</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12282-023-01498-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12282-023-01498-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids></links><search><creatorcontrib>Sanuki, Fumiaki</creatorcontrib><creatorcontrib>Mikami, Yuka</creatorcontrib><creatorcontrib>Nishimura, Hirotake</creatorcontrib><creatorcontrib>Fujita, Yoshinori</creatorcontrib><creatorcontrib>Monobe, Yasumasa</creatorcontrib><creatorcontrib>Nomura, Tsunehisa</creatorcontrib><creatorcontrib>Taira, Naruto</creatorcontrib><creatorcontrib>Moriya, Takuya</creatorcontrib><title>Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes</title><title>Breast cancer (Tokyo, Japan)</title><addtitle>Breast Cancer</addtitle><description>Background
B7 homolog 4
(
B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes.
Methods
Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor–stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression.
Results
B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28–8;
p
= 0.021), inflamed TIL pattern (
p
= 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = − 0.509,
p
< 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 (
ρ
= − 0.354,
p
< 0.001).
Conclusions
These results suggest that considering the TIL pattern and TLS and identifying the expression of PD-L1 and the basal-like type are useful for estimating B7-H4 expression. In addition, luminal androgen receptor (LAR)-type is frequently deficient in B7-H4 expression. In non-LAR types, B7-H4 and IDO1 expression are exclusive.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Cancer Research</subject><subject>Health aspects</subject><subject>Immunohistochemistry</subject><subject>Keratin</subject><subject>Lymphocytes</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><issn>1340-6868</issn><issn>1880-4233</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kc9u1DAQhyMEEqXwApwsceFQg_8ksXMsLdCVVioHOFuOd7y4SuzgcSr2NXhivA1nTjOa-X4jjb6mecvZB86Y-ohcCC0oE5Iy3g6aqmfNBdea0VZI-bz2smW0171-2bxCfGCslYr1F82f3TyvMf0MWNKUjsHZidhopxMGJMmTT4retVdkd3vPr-riQL7d0j0n8HvJgBhSfBqWdU6ZhPMpIHNwOUF8DDnFGWIho0U4kIqWHJYJaISjLeERyJjBYiHORgeZ4DqW0wL4unnh7YTw5l-9bH58-fz95o7u77_ubq731EkmC_U9Vy3Y8eDVoL3qWO9GxqXXBz1Iz2znlfDW896JzmrXC9v6VjvZMTf20g7ysnm_3V1y-rUCFjMHdDBNNkJa0Qjd6WFgqmsr-m5Dj3YCE6JPJVt3xs216odedlx3lRIbVf9HzODNksNs88lwZs6azKbJVE3mSZNRNSS3EFY4HiGbh7TmagD_l_oLXHCWZg</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>Sanuki, Fumiaki</creator><creator>Mikami, Yuka</creator><creator>Nishimura, Hirotake</creator><creator>Fujita, Yoshinori</creator><creator>Monobe, Yasumasa</creator><creator>Nomura, Tsunehisa</creator><creator>Taira, Naruto</creator><creator>Moriya, Takuya</creator><general>Springer Nature Singapore</general><general>Springer</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7357-3243</orcidid></search><sort><creationdate>20231101</creationdate><title>Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes</title><author>Sanuki, Fumiaki ; Mikami, Yuka ; Nishimura, Hirotake ; Fujita, Yoshinori ; Monobe, Yasumasa ; Nomura, Tsunehisa ; Taira, Naruto ; Moriya, Takuya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c303t-f6174eabdf798f7506cb013f8d893f0a5f72faf16c25a8c62a4f48c350cb63a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>Cancer Research</topic><topic>Health aspects</topic><topic>Immunohistochemistry</topic><topic>Keratin</topic><topic>Lymphocytes</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sanuki, Fumiaki</creatorcontrib><creatorcontrib>Mikami, Yuka</creatorcontrib><creatorcontrib>Nishimura, Hirotake</creatorcontrib><creatorcontrib>Fujita, Yoshinori</creatorcontrib><creatorcontrib>Monobe, Yasumasa</creatorcontrib><creatorcontrib>Nomura, Tsunehisa</creatorcontrib><creatorcontrib>Taira, Naruto</creatorcontrib><creatorcontrib>Moriya, Takuya</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer (Tokyo, Japan)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanuki, Fumiaki</au><au>Mikami, Yuka</au><au>Nishimura, Hirotake</au><au>Fujita, Yoshinori</au><au>Monobe, Yasumasa</au><au>Nomura, Tsunehisa</au><au>Taira, Naruto</au><au>Moriya, Takuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes</atitle><jtitle>Breast cancer (Tokyo, Japan)</jtitle><stitle>Breast Cancer</stitle><date>2023-11-01</date><risdate>2023</risdate><volume>30</volume><issue>6</issue><spage>1041</spage><epage>1053</epage><pages>1041-1053</pages><issn>1340-6868</issn><eissn>1880-4233</eissn><abstract>Background
B7 homolog 4
(
B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes.
Methods
Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor–stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression.
Results
B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28–8;
p
= 0.021), inflamed TIL pattern (
p
= 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = − 0.509,
p
< 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 (
ρ
= − 0.354,
p
< 0.001).
Conclusions
These results suggest that considering the TIL pattern and TLS and identifying the expression of PD-L1 and the basal-like type are useful for estimating B7-H4 expression. In addition, luminal androgen receptor (LAR)-type is frequently deficient in B7-H4 expression. In non-LAR types, B7-H4 and IDO1 expression are exclusive.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><doi>10.1007/s12282-023-01498-7</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7357-3243</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1340-6868 |
| ispartof | Breast cancer (Tokyo, Japan), 2023-11, Vol.30 (6), p.1041-1053 |
| issn | 1340-6868 1880-4233 |
| language | eng |
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| subjects | Analysis Apoptosis Breast cancer Cancer Research Health aspects Immunohistochemistry Keratin Lymphocytes Medicine Medicine & Public Health Oncology Original Article Surgery Surgical Oncology |
| title | Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes |
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