Impact of NK Cell Activating Receptor Gene Variants on Receptor Expression and Outcome of Immunotherapy in Acute Myeloid Leukemia

Frontiers in Immunology

卷:12

Mats Brune¹  Lovisa Wennström¹  Anna Martner²  Alexander Hallner²  Kristoffer Hellstrand²  Fredrik B. Thorén³  Brwa Ali Hussein³  Elin Bernson⁴ 

[1] Department of Hematology, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;

[2] Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;

[3] Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;

[4] Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden;

[5] Tumor Immunology (TIMM) Laboratory at Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden;

关键词: NK cell receptors;    gene variants;    single nucleotide polymorphism;    acute myeloid leukemia;    Histamine/IL-2;    Re:Mission trial;   

DOI  :  10.3389/fimmu.2021.796072

来源: DOAJ

【 摘 要 】

Natural killer cells are important effector cells in the immune response against myeloid malignancies. Previous studies show that the expression of activating NK cell receptors is pivotal for efficient recognition of blasts from patients with acute myeloid leukemia (AML) and that high expression levels impact favorably on patient survival. This study investigated the potential impact of activating receptor gene variants on NK cell receptor expression and survival in a cohort of AML patients receiving relapse-preventive immunotherapy with histamine dihydrochloride and low-dose IL-2 (HDC/IL-2). Patients harboring the G allele of rs1049174 in the KLRK1 gene encoding NKG2D showed high expression of NKG2D by CD56bright NK cells and a favorable clinical outcome in terms of overall survival. For DNAM-1, high therapy-induced receptor expression entailed improved survival, while patients with high DNAM-1 expression before immunotherapy associated with unfavorable clinical outcome. The previously reported SNPs in NCR3 encoding NKp30, which purportedly influence mRNA splicing into isoforms with discrete functions, did not affect outcome in this study. Our results imply that variations in genes encoding activating NK cell receptors determine receptor expression and clinical outcome in AML immunotherapy.

【 授权许可】

Unknown