NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance

Abstract

// Anna Martner 1 , Anna Rydström 1 , Rebecca E. Riise 1 , Johan Aurelius 1, 2 , Mats Brune 2 , Robin Foà 3 , Kristoffer Hellstrand 1 , Fredrik B. Thorén 1 1 TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden 2 Department of Hematology, University of Gothenburg, Gothenburg 413 45, Sweden 3 Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome 00161, Italy Correspondence to: Anna Martner, e-mail: anna.martner@gu.se Keywords: acute myeloid leukemia, immunotherapy, natural killer cells, NKp30, NKp46 Received: August 05, 2015      Accepted: September 08, 2015      Published: October 30, 2015 ABSTRACT In a phase IV trial, eighty-four patients (age 18–79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin-2 (IL-2) to prevent relapse in the post-consolidation phase. Aspects of natural killer (NK) cell biology were analyzed before and during immunotherapy with focus on outcome in older patients. In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56 bright and CD16 + NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. In older patients, a high expression of NKp30 or NKp46 on CD16 + NK cells before and during therapy predicted leukemia-free and overall survival. These results suggest that NK cell functions determine relapse risk and survival in older AML patients and point to biomarkers of efficacy in protocols for remission maintenance.