Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8+ Tumor-infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma

Anticancer Res. 2019 Aug;39(8):4539-4548. doi: 10.21873/anticanres.13631.

Abstract

Background/aim: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP).

Patients and methods: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8+ tumor-infiltrating lymphocytes (TILs) in pretreatment biopsy specimens-versus-surgical specimens after resection. We determined the prognostic significance of these factors.

Results: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8+ TIL density was significantly increased after neoadjuvant treatment. However, PD-L1 expression on TCs or ICs, and CD8+ TIL density, was not significantly associated with patient survival in ESCC patients.

Conclusion: NAC-FP induced PD-L1 expression on ICs and CD8+ TILs in ESCC patients. This finding suggests that PD-1/PD-L1 blockade could be combined with NAC-FP to treat ESCC patients.

Keywords: Neoadjuvant chemotherapy; esophageal cancer; programmed death-1-ligand.

MeSH terms

  • Aged
  • B7-H1 Antigen / blood
  • B7-H1 Antigen / genetics*
  • Biomarkers, Tumor / blood*
  • CD8-Positive T-Lymphocytes / drug effects
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Esophageal Squamous Cell Carcinoma / blood
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Prognosis
  • Programmed Cell Death 1 Receptor / blood
  • Programmed Cell Death 1 Receptor / genetics*
  • Tumor Microenvironment / drug effects

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Cisplatin
  • Fluorouracil