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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...

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Main Authors: Pötzsch, Max (Author) , Berg, E. (Author) , Hummel, M. (Author) , Stein, U. (Author) , Winterfeld, Moritz von (Author) , Jöhrens, K. (Author) , Rau, B. (Author) , Daum, S. (Author) , Treese, C. (Author)
Format: Article (Journal)
Language:English
Published: 20 September 2020
In: OncoImmunology
Year: 2020, Volume: 9
ISSN:2162-402X
DOI:10.1080/2162402X.2020.1824632
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/2162402X.2020.1824632
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Author Notes:M. Pötzsch, E. Berg, M. Hummel, U. Stein, M. von Winterfeld, K. Jöhrens, B. Rau, S. Daum, snd C. Treese
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Summary: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.
Item Description:Gesehen am 13.11.2020
Physical Description:Online Resource
ISSN:2162-402X
DOI:10.1080/2162402X.2020.1824632

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