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Original article
Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma
  1. Elizabeth D Thompson1,
  2. Marianna Zahurak2,
  3. Adrian Murphy3,
  4. Toby Cornish1,
  5. Nathan Cuka1,
  6. Eihab Abdelfatah4,
  7. Stephen Yang4,
  8. Mark Duncan4,
  9. Nita Ahuja4,
  10. Janis M Taube1,5,
  11. Robert A Anders1,3,
  12. Ronan J Kelly3
  1. 1Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
  2. 2Division of Biostatistics and Bioinformatics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. 3Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland, USA
  4. 4Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA
  5. 5Department of Dermatology, The Johns Hopkins Hospital, Baltimore Maryland, USA
  1. Correspondence to Dr Ronan J Kelly, The Gastroesophageal Cancer Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Bunting Blaustein Cancer Research Building I, 1650 Orleans Street, Room G93, Baltimore MD 21231, USA; rkelly25{at}jhmi.edu

Abstract

Objective Recent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. Here, we evaluate gastric and gastro-oesophageal junction (G/GEJ) adenocarcinomas for their expression of programmed death-ligand 1 (PD-L1), infiltration by CD8+ T cells and the relationship of both factors to patient survival.

Design Thirty-four resections of primary invasive G/GEJ were stained by immunohistochemistry for PD-L1 and CD8 and by DNA in situ hybridisation for Epstein–Barr virus (EBV). CD8+ T cell densities both within tumours and at the tumour–stromal interface were analysed using whole slide digital imaging. Patient survival was evaluated according to PD-L1 status and CD8 density.

Results 12% of resections showed tumour cell membranous PD-L1 expression and 44% showed expression within the immune stroma. Two cases (6%) were EBV positive, with one showing membranous PD-L1 positivity. Increasing CD8+ densities both within tumours and immune stroma was associated with increasing percentage of tumour (p=0.027) and stromal (p=0.005) PD-L1 expression. Both tumour and immune stromal PD-L1 expression and high intratumoral or stromal CD8+ T cell density (>500/mm2) were associated with worse progression-free survival (PFS) and overall survival (OS).

Conclusions PD-L1 is expressed on both tumour cells and in the immune stroma across all stages and histologies of G/GEJ. Surprisingly, we demonstrate that increasing CD8 infiltration is correlated with impaired PFS and OS. Patients with higher CD8+ T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. Further characterisation of the G/GEJ immune microenvironment may highlight targets for immune-based therapy.

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