The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia

Smith, Adam J. de; Walsh, Kyle M.; Ladner, Martha; Zhang, Siming; Xiao, Carmen; Cohen, Franziska; Moore, Theodore B.; Chokkalingam, Anand P.; Metayer, Catherine; Buffler, Patricia A.; Trachtenberg, Elizabeth; Wiemels, Joseph L.

doi:10.1182/blood-2013-11-540625

Cited by 39 publications

(28 citation statements)

References 43 publications

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“…As killer-cell immunoglobulin-like receptor (KIR)/ KIR-ligand disparity influences NK-cell lysis of leukemic cells, 51 we genotyped the NK-cell donor and target cells. KIR2DL1, KIR2DL2, and KIR2DL3 inhibitory receptors were expressed on the NK cells, whereas both 018Z and REH cells expressed ligands for KIR2DL1 (Cw*04 and Cw*06), and in addition, 018Z cells expressed HLACw*07, a KIR2DL2/3 ligand (supplemental Figure 5).…”

Section: B-cell Precursor All Cell Line 018z Secretes Endogenous Il-1mentioning

confidence: 99%

Central nervous system acute lymphoblastic leukemia: role of natural killer cells

Frishman-Levy

Shemesh

Bar-Sinai

et al. 2015

Blood

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Key Points• Increased IL-15 expression in leukemic lymphoblasts is associated with activation of NK cells.• The CNS may be an immunologic sanctuary protecting lymphoblasts from NK-cell activity.Central nervous system acute lymphoblastic leukemia (CNS-ALL) is a major clinical problem. Prophylactic therapy is neurotoxic, and a third of the relapses involve the CNS. Analysis of bone marrow (BM) diagnostic samples derived from children with subsequent CNS-ALL revealed a significantly high expression of the NKG2D and NKp44 receptors. We suggest that the CNS may be an immunologic sanctuary protected from NK-cell activity. CNS prophylactic therapy may thus be needed with emerging NK cell-based therapies against hematopoietic malignancies. (Blood. 2015;125(22):3420-3431)

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Section: B-cell Precursor All Cell Line 018z Secretes Endogenous Il-1mentioning

confidence: 99%

Central nervous system acute lymphoblastic leukemia: role of natural killer cells

Frishman-Levy

Shemesh

Bar-Sinai

et al. 2015

Blood

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“…HLA-Bw4T80 is an allotype of the HLA-Bw4 motif with a threonine at position 80, which exhibits lower affinity for KIR3DL1 compared with the HLA-Bw4 motif with an isoleucine at the same position (30). It is possible that HLA-Bw4T80 binds with KIR3DL1 to deliver inhibitory signals to NK cells, which would then enhance the ability of tumor cells to escape immune detection (31). However, a positive association of the combination of KIR3DL1/HLA-Bw4T80 with survival was not observed (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

Liu

Sansas

et al. 2016

Molecular and Clinical Oncology

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Abstract. Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population. Polymerase chain reaction with sequence-specific primers was used to type 15 KIRs at the DNA and mRNA level and 6 HLA ligands in 70 mNSCLC patients. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression model was applied for multivariate survival analysis, with the stepwise selection, to determine independent predictors of survival. It was observed that patients with KIR2DS4del gene expression at the mRNA level or HLA-Bw4T80 exhibited poor overall survival (OS). The multivariate analysis revealed that HLA-Bw4T80 and KIR2DS4del expression were independent predictors of OS. This observation indicated that the KIR/HLA ligand is a promising predictor of survival in mNSCLC and may also provide a strategy for treatment stratification and patient management. IntroductionNon-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth (1). Natural killer (NK) cells play a pivotal role in innate immunity and immunological surveillance (2). Activation of NK cells partly depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands (3). KIRs are a family of cell surface receptors expressed by NK cells and certain subpopulations of T lymphocytes. The KIR family consists of inhibitory as well as activating receptors characterized by both allelic (high numbers of variants) and haplotypic (different numbers of genes for inhibitory and activating receptors on individual chromosomes) polymorphisms (4). The ligands of KIRs are specific epitopes on HLA class I molecules (5). HLA-C allotypes fall into the C1 or C2 groups (asparagine and lysine, respectively, at position 80) that are recognized by KIR2DL2/KIR2DL3 and KIR2DL1/KIR2DS1, respectively. Two previous studies have implicated HLA-C1 and HLA-C2 as potential ligands for KIR2DS4 (6,7). KIR3DL1/KIR3DS1 recognizes HLA-Bw4 epitopes of HLA-A and HLA-B alleles, which are classified according to whether isoleucine or threonine is present at position 80 (4).An increased understanding of the complexities of the biology of the KIR/HLA system has provided opportunities to leverage NK cell function as a novel avenue of immunotherapy for cancer (8 HLA, human leukocyte antigen; NK, natural killer; NSCLC, non-small-cell lung cancer; mNSCLC, metastatic non-small-cell lung cancer; SSP-PCR, sequence-specific primer polymerase chain reaction;...

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“…1 The 212 ALL cases (including 114 Hispanic and 76 non-Hispanic white) in this study were children younger than 15 years of age enrolled in the California Childhood Leukemia Study. The controls (128 Hispanic and 86 nonHispanic) were derived from the California Department of Public Health's Genetic Disease Screening Program.…”

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confidence: 99%

“…Consistent with the German study, 9 the current study of individuals from California did not find an association between KIR polymorphisms and ALL in non-Hispanic whites. 1 As authors of all 3 studies point out, the discrepancies in their results could be due, in part, to differential accuracy of the genotyping methodology across the KIR locus, and/or small differences between the genetic background of the populations studied. 1,8,9 Although these 3 studies evaluated the KIR locus, they did not use the same genotyping methods or analyze the data in the same manner.…”

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confidence: 99%

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Genomic clues to ethnic differences in ALL

Savage

2014

Blood

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The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia

Abstract: • Carrying the KIR A/A genotype contributes to risk of childhood ALL, particularly in Hispanics.

Cited by 39 publications

References 43 publications

Central nervous system acute lymphoblastic leukemia: role of natural killer cells

Central nervous system acute lymphoblastic leukemia: role of natural killer cells

Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

Genomic clues to ethnic differences in ALL

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