Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy
We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8 + tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CR...
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Veröffentlicht in: | Oncoimmunology 2017-03, Vol.6 (3), p.e1288331-e1288331 |
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creator | Balermpas, Panagiotis Martin, Daniel Wieland, Ulrike Rave-Fränk, Margret Strebhardt, Klaus Rödel, Claus Fokas, Emmanouil Rödel, Franz |
description | We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8
+
tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16
INK4a
expression. After a median follow-up of 40 mo (1-205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8
+
and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16
INK4a
(p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial. |
doi_str_mv | 10.1080/2162402X.2017.1288331 |
format | Article |
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+
tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16
INK4a
expression. After a median follow-up of 40 mo (1-205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8
+
and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16
INK4a
(p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial.</description><identifier>ISSN: 2162-4011</identifier><identifier>ISSN: 2162-402X</identifier><identifier>EISSN: 2162-402X</identifier><identifier>DOI: 10.1080/2162402X.2017.1288331</identifier><identifier>PMID: 28405521</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Anal cancer ; HPV ; immune cell infiltration ; immunotherapy ; Original Research ; PD -1/PD-L1 ; prognostic</subject><ispartof>Oncoimmunology, 2017-03, Vol.6 (3), p.e1288331-e1288331</ispartof><rights>2017 Taylor & Francis Group, LLC 2017</rights><rights>2017 Taylor & Francis Group, LLC 2017 Taylor & Francis Group, LLC</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-54dd0ed0449e25a31a5f4cc8c2e9de2506b5d4e8db58fba8796896b8ca79d0403</citedby><cites>FETCH-LOGICAL-c534t-54dd0ed0449e25a31a5f4cc8c2e9de2506b5d4e8db58fba8796896b8ca79d0403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384387/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384387/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28405521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balermpas, Panagiotis</creatorcontrib><creatorcontrib>Martin, Daniel</creatorcontrib><creatorcontrib>Wieland, Ulrike</creatorcontrib><creatorcontrib>Rave-Fränk, Margret</creatorcontrib><creatorcontrib>Strebhardt, Klaus</creatorcontrib><creatorcontrib>Rödel, Claus</creatorcontrib><creatorcontrib>Fokas, Emmanouil</creatorcontrib><creatorcontrib>Rödel, Franz</creatorcontrib><title>Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy</title><title>Oncoimmunology</title><addtitle>Oncoimmunology</addtitle><description>We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8
+
tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16
INK4a
expression. After a median follow-up of 40 mo (1-205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8
+
and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16
INK4a
(p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial.</description><subject>Anal cancer</subject><subject>HPV</subject><subject>immune cell infiltration</subject><subject>immunotherapy</subject><subject>Original Research</subject><subject>PD -1/PD-L1</subject><subject>prognostic</subject><issn>2162-4011</issn><issn>2162-402X</issn><issn>2162-402X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNp9Uttu1DAQjRCIVqWfAPIjEuzW18ThAYG2lFZaqRUCqW_WxHa6rpx4sZNW-xH8M073IvqCH3yZOefMyHOK4i3Bc4IlPqOkpBzT2znFpJoTKiVj5EVxPMVnU-Ll4U7IUXGa0j3Oq8SiZPXr4ohKjoWg5Lj4czl20KM1rJ33oQP04OKYkA9gEPQG3ZzPyFneluQjWpzLD0_Bi-vbG4Zcnx_gkYZe25glBmf7IaEhWhisQY9uWCG9sl2IYFwYVjbCevMJ_cjAkIkWtSEi13Vjv0--KV614JM93Z0nxa-Lbz8Xl7Pl9ferxdflTAvGh5ngxmBrMOe1pQIYAdFyraWmtjY5gstGGG6laYRsG5BVXcq6bKSGqs4szE6Kq62uCXCv1tF1EDcqgFNPgRDvFMTBaW8V4xQLYhlUEvO2qgHbqiXGlBq0KOsma33eaq3HprNG5z-I4J-JPs_0bqXuwoMSTHImqyzwficQw-_RpkF1LmnrPfQ2jEkRKStOOZVT32IL1TGkFG17KEOwmpyh9s5QkzPUzhmZ9-7fHg-svQ8y4MsW4Po8lA4eQ_RGDbDxIbYxD9glxf5f4y9p78jS</recordid><startdate>20170304</startdate><enddate>20170304</enddate><creator>Balermpas, Panagiotis</creator><creator>Martin, Daniel</creator><creator>Wieland, Ulrike</creator><creator>Rave-Fränk, Margret</creator><creator>Strebhardt, Klaus</creator><creator>Rödel, Claus</creator><creator>Fokas, Emmanouil</creator><creator>Rödel, Franz</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170304</creationdate><title>Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy</title><author>Balermpas, Panagiotis ; Martin, Daniel ; Wieland, Ulrike ; Rave-Fränk, Margret ; Strebhardt, Klaus ; Rödel, Claus ; Fokas, Emmanouil ; Rödel, Franz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-54dd0ed0449e25a31a5f4cc8c2e9de2506b5d4e8db58fba8796896b8ca79d0403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anal cancer</topic><topic>HPV</topic><topic>immune cell infiltration</topic><topic>immunotherapy</topic><topic>Original Research</topic><topic>PD -1/PD-L1</topic><topic>prognostic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balermpas, Panagiotis</creatorcontrib><creatorcontrib>Martin, Daniel</creatorcontrib><creatorcontrib>Wieland, Ulrike</creatorcontrib><creatorcontrib>Rave-Fränk, Margret</creatorcontrib><creatorcontrib>Strebhardt, Klaus</creatorcontrib><creatorcontrib>Rödel, Claus</creatorcontrib><creatorcontrib>Fokas, Emmanouil</creatorcontrib><creatorcontrib>Rödel, Franz</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Oncoimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balermpas, Panagiotis</au><au>Martin, Daniel</au><au>Wieland, Ulrike</au><au>Rave-Fränk, Margret</au><au>Strebhardt, Klaus</au><au>Rödel, Claus</au><au>Fokas, Emmanouil</au><au>Rödel, Franz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy</atitle><jtitle>Oncoimmunology</jtitle><addtitle>Oncoimmunology</addtitle><date>2017-03-04</date><risdate>2017</risdate><volume>6</volume><issue>3</issue><spage>e1288331</spage><epage>e1288331</epage><pages>e1288331-e1288331</pages><issn>2162-4011</issn><issn>2162-402X</issn><eissn>2162-402X</eissn><abstract>We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8
+
tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16
INK4a
expression. After a median follow-up of 40 mo (1-205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8
+
and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16
INK4a
(p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>28405521</pmid><doi>10.1080/2162402X.2017.1288331</doi><oa>free_for_read</oa></addata></record> |
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subjects | Anal cancer HPV immune cell infiltration immunotherapy Original Research PD -1/PD-L1 prognostic |
title | Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy |
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