Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression
The prognostic potential of anti-tumor immune responses is becoming increasingly important in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S) especially regarding the use of immune checkpoint inhibitors. This study analyzes for the first time the prognostic impact of tumor-infilt...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1824632 |
| _version_ | 1818358143200002048 |
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| author | M. Pötzsch E. Berg M. Hummel U. Stein M. von Winterfeld K. Jöhrens B. Rau S. Daum C. Treese |
| author_facet | M. Pötzsch E. Berg M. Hummel U. Stein M. von Winterfeld K. Jöhrens B. Rau S. Daum C. Treese |
| author_sort | M. Pötzsch |
| collection | DOAJ |
| description | The prognostic potential of anti-tumor immune responses is becoming increasingly important in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S) especially regarding the use of immune checkpoint inhibitors. This study analyzes for the first time the prognostic impact of tumor-infiltrating lymphocytes (TILs) and checkpoint inhibitors in a large Caucasian cohort in patients with AGE/S. We screened tissue samples from 438 therapy-naïve patients with AGE/S undergoing surgery between 1992 and 2005, examined in a tissue microarray (TMA) and stained against human CD3, CD4, CD8, PD-1, and PD-L1. Out of 438 tissue samples, 210 were eligible for multivariate analysis. This revealed that high infiltration with CD3+, CD4+, or CD8+ TILs was associated with an increased overall survival in AGE/S patients, which could only be confirmed in multivariate analysis for CD3 (HR: 0.326; p = .023). Independent improved survival was limited to gastric cancer patients and to early tumor stages as long as TILs did not express PD-1 (HR: 1.522; p = .021). Subgroup analyses indicate that TIL-dependent anti-tumor immune response is only effective in gastric cancer patients in early stages of disease in PD-1 negative TILs. Combined analysis of PD-1 and CD3 could serve as a prognostic marker for the clinical outcome of gastric cancer patients and could also be of interest for immunotherapy. |
| first_indexed | 2024-12-13T20:24:19Z |
| format | Article |
| id | doaj.art-e7dbafdddfde423bab4613d04e42b888 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T20:24:19Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-e7dbafdddfde423bab4613d04e42b8882022-12-21T23:32:36ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.18246321824632Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expressionM. Pötzsch0E. Berg1M. Hummel2U. Stein3M. von Winterfeld4K. Jöhrens5B. Rau6S. Daum7C. Treese8Humboldt-Universität zu Berlin and Berlin Institute of HealthHumboldt-Universität zu Berlin and Berlin Institute of HealthHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz AssociationUniversity Hospital HeidelbergUniversity Carl Gustav CarusHumboldt-Universität zu Berlin and Berlin Institute of HealthHumboldt-Universität zu Berlin and Berlin Institute of HealthHumboldt-Universität zu Berlin and Berlin Institute of HealthThe prognostic potential of anti-tumor immune responses is becoming increasingly important in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S) especially regarding the use of immune checkpoint inhibitors. This study analyzes for the first time the prognostic impact of tumor-infiltrating lymphocytes (TILs) and checkpoint inhibitors in a large Caucasian cohort in patients with AGE/S. We screened tissue samples from 438 therapy-naïve patients with AGE/S undergoing surgery between 1992 and 2005, examined in a tissue microarray (TMA) and stained against human CD3, CD4, CD8, PD-1, and PD-L1. Out of 438 tissue samples, 210 were eligible for multivariate analysis. This revealed that high infiltration with CD3+, CD4+, or CD8+ TILs was associated with an increased overall survival in AGE/S patients, which could only be confirmed in multivariate analysis for CD3 (HR: 0.326; p = .023). Independent improved survival was limited to gastric cancer patients and to early tumor stages as long as TILs did not express PD-1 (HR: 1.522; p = .021). Subgroup analyses indicate that TIL-dependent anti-tumor immune response is only effective in gastric cancer patients in early stages of disease in PD-1 negative TILs. Combined analysis of PD-1 and CD3 could serve as a prognostic marker for the clinical outcome of gastric cancer patients and could also be of interest for immunotherapy.http://dx.doi.org/10.1080/2162402X.2020.1824632gastric cancertumor-infiltrating lymphocytespd-1biomarker |
| spellingShingle | M. Pötzsch E. Berg M. Hummel U. Stein M. von Winterfeld K. Jöhrens B. Rau S. Daum C. Treese Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression OncoImmunology gastric cancer tumor-infiltrating lymphocytes pd-1 biomarker |
| title | Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression |
| title_full | Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression |
| title_fullStr | Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression |
| title_full_unstemmed | Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression |
| title_short | Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression |
| title_sort | better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by pd 1 expression |
| topic | gastric cancer tumor-infiltrating lymphocytes pd-1 biomarker |
| url | http://dx.doi.org/10.1080/2162402X.2020.1824632 |
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