Associations of epstein-barr virus-positive gastric adenocarcinoma with circulating mediators of inflammation and immune response

M. Constanza Camargo*, Armands Sivins, Sergejs Isajevs, Valdis Folkmanis, Dace Rudzīte, Margaret L. Gulley, G. Johan Offerhaus, Marcis Leja, Charles S. Rabkin

*Corresponding author for this work

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Abstract

Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR = 3.4; p-trend = 0.004), interleukin (IL)-10 (OR = 2.4; p-trend = 0.019), CCL19 (OR = 2.3; p-trend = 0.019), CCL11 (OR = 2.2; p-trend = 0.026), IL-17A (OR = 2.0; p-trend = 0.038) and CCL8 (OR = 1.9; p-trend = 0.049). Systemic responses to EBV-positive gastric cancer are characterized by alterations in chemokines and PD-L1. Profiling of these molecules may enable non-invasive diagnosis of EBV status when tumor tissue is unavailable. Our findings provide theoretical justification for clinical evaluations of immune checkpoint therapy for EBV-positive gastric cancer.

Original languageEnglish
Article number284
JournalCancers
Volume10
Issue number9
DOIs
Publication statusPublished - 1 Sept 2018

Keywords

  • Chemokines
  • EBV
  • Gastric cancer
  • Inflammation
  • PD-L1

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