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Sci Rep. 2018 Sep 17;8(1):13887. doi: 10.1038/s41598-018-32299-0.

Computational measurement of tumor immune microenvironment in gastric adenocarcinomas.

Author information

1
Department of Biomedical Engineering and Computational Biology Program, Oregon Health and Science University (OHSU), Portland, OR, 97239, USA.
2
The Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
3
Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
5
Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kkmkys@skku.edu.

Abstract

The use of four groups of tumor immune microenvironments (TME) based on PD-L1 and tumor-infiltrating T lymphocytes (TIL) is a reliable biomarker for anti-PD-1/PD-L1 inhibitor therapy. We classified the TME in 241 gastric cancers which were subdivided according to 40 EBV+, 76 microsatellite instability-high (MSI-H), and 125 EBV-/microsatellite-stable (MSS) subtypes by quantitative image analysis (QIA) and correlated the results with mRNA expression levels. The mean PD-L1 ratio and CD8 ratio in EBV+, MSI-H, and EBV-/MSS GCs were significantly different (P < 0.006). The PD-L1 ratio and CD8 ratio obtained by QIA correlated well with the RNA levels of PD-L1 (r = 0.63) and CD8 (r = 0.67), respectively. The TME were type I (PD-L1H/CD8H) in 45, type II (PD-L1L/CD8L) in 106, type III (PD-L1H/CD8L) in 8, and type IV (PD-L1L/CD8H) in 82 cases. The type I TME was significantly associated with high TIL (P = 3.0E-11) and EBV+ status (P = 8.55E-08). In conclusion, QIA results correlated well with the mRNA expression levels and classified TME of gastric cancers.

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