Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients

Xiaofang Xing, Jianping Guo, Xianzi Wen, Guangyu Ding, Bo Li, Bin Dong, Qin Feng, Shen Li, Jian Zhang, Xiaojing Cheng, Ting Guo, Hong Du, Ying Hu, Xiaohong Wang, Lin Li, Qingda Li, Meng Xie, Liting Li, Xiangyu Gao, Fei ShanZiyu Li, Xiaomin Ying, Tao Zhou, Jiping Wang, Jiafu Ji

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis. Correlation with clinical features and outcome were analyzed after controlling for potential confounders including EBV infection, HER2, C-met and PCNA expression. 37.8% of the cases showed membranous PD-L1 expression in tumor cells and 74.9% in infiltrating immune cells. PDL1 expression rate was rather higher in patients without metastasis, in EBV positive group and those with C-met and PCNA expression. GC patients with high level PDL1 expression exhibited better survival. GC Patients with higher T cell infiltration also showed elevated PDL1, PDL2 and PD1 expression and predict favorable outcome, indicating an adaptive immune resistance mechanism may exist. The group of patients infiltrated with lower density CD3+ T cells also without PDL1 expression in tumor cells predict the worst outcome in the subgroup of different PTNM stage, which may suggest an inactive immune status. These results highlights the need to assess both PDL1 expression in all tumor context and the characterization of the GC immune microenvironment.

Original languageEnglish (US)
Article numbere1356144
JournalOncoImmunology
Volume7
Issue number3
DOIs
StatePublished - Mar 4 2018

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Keywords

  • gastric cancer
  • PD1
  • PDL1
  • PDL2
  • prognosis
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Xing, X., Guo, J., Wen, X., Ding, G., Li, B., Dong, B., Feng, Q., Li, S., Zhang, J., Cheng, X., Guo, T., Du, H., Hu, Y., Wang, X., Li, L., Li, Q., Xie, M., Li, L., Gao, X., ... Ji, J. (2018). Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients. OncoImmunology, 7(3), [e1356144]. https://doi.org/10.1080/2162402X.2017.1356144