Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis
Prognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinica...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2020.00144/full |
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| author | Silvio Däster Serenella Eppenberger-Castori Valentina Mele Hannah M. Schäfer Lukas Schmid Benjamin Weixler Savas D. Soysal Raoul A. Droeser Giulio C. Spagnoli Christoph Kettelhack Daniel Oertli Luigi Terracciano Luigi Tornillo Urs von Holzen Urs von Holzen Urs von Holzen |
| author_facet | Silvio Däster Serenella Eppenberger-Castori Valentina Mele Hannah M. Schäfer Lukas Schmid Benjamin Weixler Savas D. Soysal Raoul A. Droeser Giulio C. Spagnoli Christoph Kettelhack Daniel Oertli Luigi Terracciano Luigi Tornillo Urs von Holzen Urs von Holzen Urs von Holzen |
| author_sort | Silvio Däster |
| collection | DOAJ |
| description | Prognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinical significance of PD-1 and PD-L1 expression in gastric and esophageal adenocarcinomas, particularly in non-Asian patients, is still unclear. Three tissue microarrays including 190 clinically annotated esophageal (n = 31) and gastric (n = 159) adenocarcinomas and 58 paired mucosa specimens, were stained with PD-1, PD-L1, and CD8-specific reagents in indirect immunohistochemistry assays. PD-L1 expression was detectable in 23.2% of cancer specimens. High PD-1 expression was detectable in 37.3% of cases and high CD8+ infiltration in 76%. PD-L1 and high PD1 expression significantly correlated with each other (rs = 0.404, P < 0.0001) and both significantly correlated with CD8+ infiltration (rs = 0.435, P = 0.0003, and rs = 0.444; P = 0.0004, respectively). CD8+ lymphocyte infiltration correlated with improved survival in univariate (P = 0.009), but not multivariate analysis. Most interestingly, multivariate analysis and Kaplan-Meier curves indicate that combined low PD-1/PD-L1 expression and low CD8+ lymphocyte infiltration significantly correlate with poor prognosis. Our data document the clinical significance of a microenvironmental signature including PD-1/PD-L1 expression and CD8+ lymphocyte infiltration in gastric and esophageal adenocarcinomas and contribute to identify a patients' subset requiring more aggressive peri-operative treatments. |
| first_indexed | 2024-12-11T21:23:29Z |
| format | Article |
| id | doaj.art-4751443826274a429cf6b643bb3a11d0 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-11T21:23:29Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-4751443826274a429cf6b643bb3a11d02022-12-22T00:50:23ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-04-01710.3389/fmed.2020.00144470364Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe PrognosisSilvio Däster0Serenella Eppenberger-Castori1Valentina Mele2Hannah M. Schäfer3Lukas Schmid4Benjamin Weixler5Savas D. Soysal6Raoul A. Droeser7Giulio C. Spagnoli8Christoph Kettelhack9Daniel Oertli10Luigi Terracciano11Luigi Tornillo12Urs von Holzen13Urs von Holzen14Urs von Holzen15Department of Surgery, University Hospital Basel, Basel, SwitzerlandDivision of Molecular Pathology, Institute of Pathology, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandNational Research Council, Institute of Translational Pharmacology, Rome, ItalyDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandDivision of Molecular Pathology, Institute of Pathology, University Hospital Basel, Basel, SwitzerlandDivision of Molecular Pathology, Institute of Pathology, University Hospital Basel, Basel, SwitzerlandDepartment of Surgery, University Hospital Basel, Basel, SwitzerlandHarper Cancer Research Institute, Indiana University School of Medicine South Bend, South Bend, IN, United StatesGoshen Center for Cancer Care, Goshen, IN, United StatesPrognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinical significance of PD-1 and PD-L1 expression in gastric and esophageal adenocarcinomas, particularly in non-Asian patients, is still unclear. Three tissue microarrays including 190 clinically annotated esophageal (n = 31) and gastric (n = 159) adenocarcinomas and 58 paired mucosa specimens, were stained with PD-1, PD-L1, and CD8-specific reagents in indirect immunohistochemistry assays. PD-L1 expression was detectable in 23.2% of cancer specimens. High PD-1 expression was detectable in 37.3% of cases and high CD8+ infiltration in 76%. PD-L1 and high PD1 expression significantly correlated with each other (rs = 0.404, P < 0.0001) and both significantly correlated with CD8+ infiltration (rs = 0.435, P = 0.0003, and rs = 0.444; P = 0.0004, respectively). CD8+ lymphocyte infiltration correlated with improved survival in univariate (P = 0.009), but not multivariate analysis. Most interestingly, multivariate analysis and Kaplan-Meier curves indicate that combined low PD-1/PD-L1 expression and low CD8+ lymphocyte infiltration significantly correlate with poor prognosis. Our data document the clinical significance of a microenvironmental signature including PD-1/PD-L1 expression and CD8+ lymphocyte infiltration in gastric and esophageal adenocarcinomas and contribute to identify a patients' subset requiring more aggressive peri-operative treatments.https://www.frontiersin.org/article/10.3389/fmed.2020.00144/fullgastric canceresophageal cancerPD-1PD-L1CD8+ lymphocyte infiltration |
| spellingShingle | Silvio Däster Serenella Eppenberger-Castori Valentina Mele Hannah M. Schäfer Lukas Schmid Benjamin Weixler Savas D. Soysal Raoul A. Droeser Giulio C. Spagnoli Christoph Kettelhack Daniel Oertli Luigi Terracciano Luigi Tornillo Urs von Holzen Urs von Holzen Urs von Holzen Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis Frontiers in Medicine gastric cancer esophageal cancer PD-1 PD-L1 CD8+ lymphocyte infiltration |
| title | Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis |
| title_full | Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis |
| title_fullStr | Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis |
| title_full_unstemmed | Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis |
| title_short | Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis |
| title_sort | low expression of programmed death 1 pd 1 pd 1 ligand 1 pd l1 and low cd8 t lymphocyte infiltration identify a subgroup of patients with gastric and esophageal adenocarcinoma with severe prognosis |
| topic | gastric cancer esophageal cancer PD-1 PD-L1 CD8+ lymphocyte infiltration |
| url | https://www.frontiersin.org/article/10.3389/fmed.2020.00144/full |
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