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.
Highlights
Tumor Epstein-Barr virus (EBV) positivity defines one of four major molecular subtypes of gastric cancer in The Cancer Genome Atlas (TCGA) [1]
We examined mRNA levels of these eight markers in tumor tissue of 24 EBV-positive and
CC-chemokine is known to be up-regulated in tumor tissue of nasopharyngeal carcinoma (NPC) and some EBV-associated lymphomas, and is induced by EBV nuclear antigen tumor tissue
Summary
Tumor Epstein-Barr virus (EBV) positivity defines one of four major molecular subtypes of gastric cancer in The Cancer Genome Atlas (TCGA) [1]. EBV status is not routinely determined in clinical practice since tailored therapies are not currently available. EBV-positive gastric cancer is characterized by prominent inflammatory infiltrate, consisting primarily of CD8-positive or CD4-positive T cells [2,3]. We hypothesized that EBV status in cancer tissue may be reflected in profiles of circulating mediators of inflammation and immune response.
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