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Cancers 2018, 10(9), 284;

Associations of Epstein-Barr Virus-Positive Gastric Adenocarcinoma with Circulating Mediators of Inflammation and Immune Response

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr., BG 9609/6E338, Bethesda, MD 20892, USA
Institute of Clinical and Preventive Medicine and Faculty of Medicine, University of Latvia, LV1586 Riga, Latvia
Department of Pathology, University of North Carolina, Chapel Hill, NC 27599, USA
Department of Pathology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Author to whom correspondence should be addressed.
Received: 6 July 2018 / Revised: 16 August 2018 / Accepted: 20 August 2018 / Published: 23 August 2018
(This article belongs to the Special Issue Epstein–Barr Virus Associated Cancers)
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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. View Full-Text
Keywords: chemokines; EBV; gastric cancer; inflammation; PD-L1 chemokines; EBV; gastric cancer; inflammation; PD-L1

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Camargo, M.C.; Sivins, A.; Isajevs, S.; Folkmanis, V.; Rudzīte, D.; Gulley, M.L.; Offerhaus, G.J.; Leja, M.; Rabkin, C.S. Associations of Epstein-Barr Virus-Positive Gastric Adenocarcinoma with Circulating Mediators of Inflammation and Immune Response. Cancers 2018, 10, 284.

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