Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival
PD‐L1 immune checkpoint inhibitor expression was evaluated in high‐grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who u...
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| Veröffentlicht in: | APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2021-05, Vol.129 (5), p.254-264 |
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| creator | Bansal, Akriti Srinivasan, Radhika Rohilla, Manish Rai, Bhavana Rajwanshi, Arvind Suri, Vanita Chandra Saha, Subhas |
| description | PD‐L1 immune checkpoint inhibitor expression was evaluated in high‐grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC‐PC) were selected. In HGSC‐PC cases, the pre‐NACT ascitic fluid cell blocks were included. Tumor‐infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor‐associated macrophages (TAMs), PD‐1 and PD‐L1 expression. HGSC‐post‐chemotherapy showed increased TILs, predominantly CD8+T‐lymphocytes, compared to HGSC‐U. HGSC showed PD‐L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD‐L1 expression was seen in matched pre‐ and post‐NACT tumor cells. HGSC‐PC showed higher expression of PD‐L1. There was no association of PD‐L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD‐L1 CPS at 10%, immunotype I (PD‐L1+/CD‐8+), corresponding to tumors with adaptive immune evasion, showed worst disease‐free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD‐L1+/CD8−). Immunotyping based on PD‐L1/CD8+ expression correlates to prognosis and outcome. |
| doi_str_mv | 10.1111/apm.13116 |
| format | Article |
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Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC‐PC) were selected. In HGSC‐PC cases, the pre‐NACT ascitic fluid cell blocks were included. Tumor‐infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor‐associated macrophages (TAMs), PD‐1 and PD‐L1 expression. HGSC‐post‐chemotherapy showed increased TILs, predominantly CD8+T‐lymphocytes, compared to HGSC‐U. HGSC showed PD‐L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD‐L1 expression was seen in matched pre‐ and post‐NACT tumor cells. HGSC‐PC showed higher expression of PD‐L1. There was no association of PD‐L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD‐L1 CPS at 10%, immunotype I (PD‐L1+/CD‐8+), corresponding to tumors with adaptive immune evasion, showed worst disease‐free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD‐L1+/CD8−). Immunotyping based on PD‐L1/CD8+ expression correlates to prognosis and outcome.</description><identifier>ISSN: 0903-4641</identifier><identifier>EISSN: 1600-0463</identifier><identifier>DOI: 10.1111/apm.13116</identifier><identifier>PMID: 33455015</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Ascitic fluid ; B7-H1 Antigen - metabolism ; Biomarkers, Tumor - metabolism ; CD4 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - pathology ; Chemotherapy ; Chemotherapy, Adjuvant ; Cystadenocarcinoma, Serous - drug therapy ; Cystadenocarcinoma, Serous - immunology ; Cystadenocarcinoma, Serous - pathology ; Cystadenocarcinoma, Serous - surgery ; Cytoreduction Surgical Procedures ; Disease-Free Survival ; Female ; High‐grade serous carcinoma ; Humans ; Immune checkpoint inhibitors ; Immunohistochemistry ; Immunophenotyping ; immunotyping ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating - metabolism ; Lymphocytes, Tumor-Infiltrating - pathology ; Macrophages ; Medical prognosis ; Middle Aged ; Neoadjuvant Therapy ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - immunology ; Ovarian Neoplasms - pathology ; Ovarian Neoplasms - surgery ; ovary ; PD-L1 protein ; PD‐L1 ; Prognosis ; Quality ; Surgery ; Survival ; T-Lymphocyte Subsets - metabolism ; T-Lymphocyte Subsets - pathology ; Tumor cells ; tumor microenvironment ; Tumor Microenvironment - immunology ; Tumor-Associated Macrophages - metabolism ; Tumor-Associated Macrophages - pathology ; Tumors</subject><ispartof>APMIS : acta pathologica, microbiologica et immunologica Scandinavica, 2021-05, Vol.129 (5), p.254-264</ispartof><rights>2021 APMIS. 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Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2021 APMIS Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3536-bd301f2adb16fad9f407dda1f7b5368867b7b0afd3c5834bdaa0129b76166e913</citedby><cites>FETCH-LOGICAL-c3536-bd301f2adb16fad9f407dda1f7b5368867b7b0afd3c5834bdaa0129b76166e913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapm.13116$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapm.13116$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33455015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bansal, Akriti</creatorcontrib><creatorcontrib>Srinivasan, Radhika</creatorcontrib><creatorcontrib>Rohilla, Manish</creatorcontrib><creatorcontrib>Rai, Bhavana</creatorcontrib><creatorcontrib>Rajwanshi, Arvind</creatorcontrib><creatorcontrib>Suri, Vanita</creatorcontrib><creatorcontrib>Chandra Saha, Subhas</creatorcontrib><title>Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival</title><title>APMIS : acta pathologica, microbiologica et immunologica Scandinavica</title><addtitle>APMIS</addtitle><description>PD‐L1 immune checkpoint inhibitor expression was evaluated in high‐grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC‐PC) were selected. In HGSC‐PC cases, the pre‐NACT ascitic fluid cell blocks were included. Tumor‐infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor‐associated macrophages (TAMs), PD‐1 and PD‐L1 expression. HGSC‐post‐chemotherapy showed increased TILs, predominantly CD8+T‐lymphocytes, compared to HGSC‐U. HGSC showed PD‐L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD‐L1 expression was seen in matched pre‐ and post‐NACT tumor cells. HGSC‐PC showed higher expression of PD‐L1. There was no association of PD‐L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD‐L1 CPS at 10%, immunotype I (PD‐L1+/CD‐8+), corresponding to tumors with adaptive immune evasion, showed worst disease‐free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD‐L1+/CD8−). Immunotyping based on PD‐L1/CD8+ expression correlates to prognosis and outcome.</description><subject>Adult</subject><subject>Aged</subject><subject>Ascitic fluid</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>Chemotherapy</subject><subject>Chemotherapy, Adjuvant</subject><subject>Cystadenocarcinoma, Serous - drug therapy</subject><subject>Cystadenocarcinoma, Serous - immunology</subject><subject>Cystadenocarcinoma, Serous - pathology</subject><subject>Cystadenocarcinoma, Serous - surgery</subject><subject>Cytoreduction Surgical Procedures</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>High‐grade serous carcinoma</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Immunohistochemistry</subject><subject>Immunophenotyping</subject><subject>immunotyping</subject><subject>Lymphocytes</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Lymphocytes, Tumor-Infiltrating - pathology</subject><subject>Macrophages</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian Neoplasms - surgery</subject><subject>ovary</subject><subject>PD-L1 protein</subject><subject>PD‐L1</subject><subject>Prognosis</subject><subject>Quality</subject><subject>Surgery</subject><subject>Survival</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>T-Lymphocyte Subsets - pathology</subject><subject>Tumor cells</subject><subject>tumor microenvironment</subject><subject>Tumor Microenvironment - immunology</subject><subject>Tumor-Associated Macrophages - metabolism</subject><subject>Tumor-Associated Macrophages - pathology</subject><subject>Tumors</subject><issn>0903-4641</issn><issn>1600-0463</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1q3DAUhUVoaaZpF3mBIOgmpTiRRrJsL8OkP4EJySJdiytLnlGwLVeyJ3iXvkGfsU_S207SRaF3Iy7n43CPDiHHnJ1xnHMYujMuOFcHZMEVYxmTSrwgC1YxkUkl-SF5ndI9Y3xZquIVORRC5jnj-YJ8v-q6qQ_jPPh-Q31Px8mEn48_wg6ih55u_WaL6yaCdTS5GKZEa4i170MH1Mz09hLlNafQW7q6LD_QO9zbuRu2oZ5Hl-gQnfX1mKj1yUFyKDfRodkUd34H7RvysoE2ubdP7xH5-unj3epLtr75fLW6WGe1yIXKjBWMN0uwhqsGbNVIVlgLvCkMyiXmMoVh0FhR56WQxgJg3MoUiivlKi6OyOned4jh2-TSqDufate20DtMpZeyKIsix59D9N0_6H2YYo_X6WXOhRS5FBVS7_dUHUNK0TV6iL6DOGvO9O9eNPai__SC7MmT42Q6Z_-Sz0UgcL4HHnzr5v876Yvb673lL2ginGs</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Bansal, Akriti</creator><creator>Srinivasan, Radhika</creator><creator>Rohilla, Manish</creator><creator>Rai, Bhavana</creator><creator>Rajwanshi, Arvind</creator><creator>Suri, Vanita</creator><creator>Chandra Saha, Subhas</creator><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>202105</creationdate><title>Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival</title><author>Bansal, Akriti ; 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Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC‐PC) were selected. In HGSC‐PC cases, the pre‐NACT ascitic fluid cell blocks were included. Tumor‐infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor‐associated macrophages (TAMs), PD‐1 and PD‐L1 expression. HGSC‐post‐chemotherapy showed increased TILs, predominantly CD8+T‐lymphocytes, compared to HGSC‐U. HGSC showed PD‐L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD‐L1 expression was seen in matched pre‐ and post‐NACT tumor cells. HGSC‐PC showed higher expression of PD‐L1. There was no association of PD‐L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD‐L1 CPS at 10%, immunotype I (PD‐L1+/CD‐8+), corresponding to tumors with adaptive immune evasion, showed worst disease‐free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD‐L1+/CD8−). Immunotyping based on PD‐L1/CD8+ expression correlates to prognosis and outcome.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33455015</pmid><doi>10.1111/apm.13116</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult Aged Ascitic fluid B7-H1 Antigen - metabolism Biomarkers, Tumor - metabolism CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - pathology Chemotherapy Chemotherapy, Adjuvant Cystadenocarcinoma, Serous - drug therapy Cystadenocarcinoma, Serous - immunology Cystadenocarcinoma, Serous - pathology Cystadenocarcinoma, Serous - surgery Cytoreduction Surgical Procedures Disease-Free Survival Female High‐grade serous carcinoma Humans Immune checkpoint inhibitors Immunohistochemistry Immunophenotyping immunotyping Lymphocytes Lymphocytes, Tumor-Infiltrating - metabolism Lymphocytes, Tumor-Infiltrating - pathology Macrophages Medical prognosis Middle Aged Neoadjuvant Therapy Ovarian Neoplasms - drug therapy Ovarian Neoplasms - immunology Ovarian Neoplasms - pathology Ovarian Neoplasms - surgery ovary PD-L1 protein PD‐L1 Prognosis Quality Surgery Survival T-Lymphocyte Subsets - metabolism T-Lymphocyte Subsets - pathology Tumor cells tumor microenvironment Tumor Microenvironment - immunology Tumor-Associated Macrophages - metabolism Tumor-Associated Macrophages - pathology Tumors |
| title | Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival |
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