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Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia

Journal article
Authors Elin Bernson
Alexander Hallner
Frida Ewald Sander
Malin Nicklasson
Malin S. Nilsson
Karin Christenson
Ebru Aydin
Jan-Åke Liljeqvist
Mats Brune
R. Foa
Johan Aurelius
Anna Martner
Kristoffer Hellstrand
Fredrik Bergh Thorén
Published in Cancer Immunology Research
Volume 6
Issue 9
Pages 1110-1119
ISSN 2326-6066
Publication year 2018
Published at Sahlgrenska Cancer Center
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Biomedicine, Department of Infectious Medicine
Pages 1110-1119
Language en
Links dx.doi.org/10.1158/2326-6066.cir-17...
Keywords NATURAL-KILLER-CELLS; RELAPSE RISK EVIDENCE; CLASS-I MOLECULES; COMPLEX CLASS-I; MHC CLASS-I; INHIBITORY RECEPTORS; DOWN-REGULATION; HLA GENOTYPES; TRANSPLANTATION; INFECTION
Subject categories Immunology in the medical area, Cancer and Oncology

Abstract

Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to affect favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The impact of CMV infection and adaptive-like NK cells on relapse and survival of patients with AML not receiving allo-SCT remains unknown. We assayed CMV IgG serostatus to determine past CMV infection in 81 nontransplanted AML patients who were receiving relapse-prevention immunotherapy comprising histamine dihydrochloride and low-dose interleukin-2 (HDC/IL2; NCT01347996). CMV seropositivity correlated negatively with leukemia-free and overall survival of patients receiving HDC/IL2, but did not correlate with outcomes in a contemporary control cohort. Analysis of outcome after stratification of patients based on concordant or discordant killer immunoglobulin-like receptor (KIR) and HLA genotypes implied that the negative impact of CMV seropositivity was restricted to patients lacking a ligand to inhibitory KIRs (iKIR). Previous CMV infection was also associated with fewer NK cells expressing only nonself iKIRs (NS-iKIR). We propose that CMV-driven NK cell education depletes the population of NS-iKIR NK cells, which in turn reduces the clinical benefit of relapse-preventive immunotherapy in AML.

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