Differential prognostic impact of CD8+ T cells based on human leucocyte antigen I and PD-L1 expression in microsatellite-unstable gastric cancer

Br J Cancer. 2020 Apr;122(9):1399-1408. doi: 10.1038/s41416-020-0793-y. Epub 2020 Mar 17.

Abstract

Background: The aim of the study was to determine the human leucocyte antigen class-I (HLA-I), programmed death-ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) of microsatellite instability-high gastric cancer.

Methods: The HLA-I expression type was determined by immunohistochemistry of HLA-A, HLA-B, HLA-C and β2-microglobulin in the centre of the tumour (CT) and in the invasive margin (IM) of samples from 293 patients (total loss vs. preserved type). PD-L1 expression and TIL density was examined immunohistochemically. HLA-I genotyping was also performed.

Results: The expression loss of the HLA-I molecules was significantly associated with low TIL density. According to survival analyses, the HLA-I expression type and PD-L1 positivity were not independent prognostic factors. The TIL density had no prognostic implication when survival analysis was performed for the whole patient group; however, high CD8+ TIL infiltration was significantly associated with good prognosis in only HLA-I-preserved-type/PD-L1-positive group (p = 0.034). The homozygosity of the HLA-I allele was more frequently observed in the total loss type group.

Conclusions: We confirmed differential prognostic implication of CD8+ TILs according to the HLA-I and PD-L1 expression. Determination of the HLA-I expression could be helpful to select patients who would benefit from anti-PD-1/PD-L1 therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Disease-Free Survival
  • Female
  • Genotype
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / immunology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Histocompatibility Antigens Class I
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor