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

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. Cancer Immunol Res; 6(9); 1110-9. ©2018 AACR.

• Authors: Elin Bernson, Alexander Hallner, Frida E Sander, Malin Nicklasson, Malin S Nilsson, Karin Christenson, Ebru Aydin, Jan-Åke Liljeqvist, Mats Brune, Robin Foà, Johan Aurelius, Anna Martner, Kristoffer Hellstrand, Fredrik B Thorén
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 6 Issue 9 Pg. 1110-1119 (09 2018) ISSN: 2326-6074 [Electronic] United States
• PMID: 29980537 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• Antibodies, Viral
• HLA Antigens
• Interleukin-2
• Receptors, KIR
• Histamine

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Viral (blood)
• Cytomegalovirus
• Cytomegalovirus Infections (immunology)
• Female
• HLA Antigens (genetics)
• Histamine (therapeutic use)
• Humans
• Immunotherapy
• Interleukin-2 (therapeutic use)
• Killer Cells, Natural (immunology)
• Leukemia, Myeloid, Acute (immunology, therapy)
• Male
• Middle Aged
• Receptors, KIR (genetics)
• Young Adult