Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with solid tumors

Omar, Suliman Al; Middleton, Derek; Marshall, Ernie; Porter, Dawn; Xinarianos, George; Raji, Olaide Y.; Field, John K.; Christmas, Stephen E.

doi:10.1016/j.humimm.2010.06.019

Cited by 52 publications

(46 citation statements)

References 40 publications

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“…Similar result was recently reported by Al Omar et al [6], the only independent study on KIR genetics in this disease published so far. However, we show here a possible protective effect of HLA-C C1C2 genotype on susceptibility to NSCLC, and association of KIR2DL2/KIR2DS2/C1C1 genotype with better response to therapy and longer survival.…”

Section: Discussionsupporting

confidence: 91%

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KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population

Wiśniewski

Jankowska²,

Passowicz−Muszyńska³

et al. 2012

Human Immunology

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Section: Discussionsupporting

confidence: 91%

“…The effect of the KIR and its ligand (HLA-I) genotype on susceptibility to non-small cell lung cancer has been only very recently examined [6,7]. Therefore, we studied here whether KIR and/or KIR ligand genotype is associated with NSCLC, its clinical manifestations, or susceptibility to treatment.…”

Section: Introductionmentioning

confidence: 99%

KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population

Wiśniewski

Jankowska²,

Passowicz−Muszyńska³

et al. 2012

Human Immunology

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“…Possession of a KIR3DL1 + and HLA-Bw4 + genotype was associated with increased incidence of kidney cancer (76), and possession of a KIR3DL1/3DL1 and HLA-Bw4 + genotype was associated with increased incidence of chronic lymphocytic leukemia (77). Among individuals with KIR3DL1 and HLA-Bw4, patients with colon cancer were enriched for HLA-Bw4-80Ile, whereas patients with other solid tumors were enriched for HLA-Bw4-80Thr (76). Possession of a KIR2DL3 + and HLA-C1/C1 genotype was previously associated with a decreased incidence of non-small-cell lung carcinoma and kidney cancer (76), whereas possession of a KIR2DL2/3 and HLA-C1…”

Section: Discussionmentioning

confidence: 98%

“…Among individuals with KIR3DL1 and HLA-Bw4, patients with colon cancer were enriched for HLA-Bw4-80Ile, whereas patients with other solid tumors were enriched for HLA-Bw4-80Thr (76). Possession of a KIR2DL3 + and HLA-C1/C1 genotype was previously associated with a decreased incidence of non-small-cell lung carcinoma and kidney cancer (76), whereas possession of a KIR2DL2/3 and HLA-C1…”

Section: Discussionmentioning

confidence: 99%

KIR and HLA Genotypes Predictive of Low-Affinity Interactions Are Associated with Lower Relapse in Autologous Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Marra

Greene

Hwang

et al. 2015

The Journal of Immunology

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Killer cell Ig–like receptors (KIRs) bind cognate HLA class I ligands with distinct affinities, affecting NK cell licensing and inhibition. We hypothesized that differences in KIR and HLA class I genotypes predictive of varying degrees of receptor–ligand binding affinities influence clinical outcomes in autologous hematopoietic cell transplantation (AHCT) for acute myeloid leukemia (AML). Using genomic DNA from a homogeneous cohort of 125 AML patients treated with AHCT, we performed KIR and HLA class I genotyping and found that patients with a compound KIR3DL1+ and HLA-Bw4-80Thr+, HLA-Bw4-80Ile– genotype, predictive of low-affinity interactions, had a low incidence of relapse, compared with patients with a KIR3DL1+ and HLA-Bw4-80Ile+ genotype, predictive of high-affinity interactions (hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.06–0.78; p = 0.02). This effect was influenced by HLA-Bw4 copy number, such that relapse progressively increased with one copy of HLA-Bw4-80Ile (HR, 1.6; 95% CI, 0.84–3.1; p = 0.15) to two to three copies (HR, 3.0; 95% CI, 1.4–6.5; p = 0.005) and progressively decreased with one to two copies of HLA-Bw4-80Thr (p = 0.13). Among KIR3DL1+ and HLA-Bw4-80Ile+ patients, a predicted low-affinity KIR2DL2/3+ and HLA-C1/C1 genotype was associated with lower relapse than a predicted high-affinity KIR2DL1+ and HLA-C2/C2 genotype (HR, 0.25; 95% CI, 0.09–0.73; p = 0.01). Similarly, a KIR3DL1+ and HLA-Bw4-80Thr+, HLA-Bw4-80Ile– genotype, or lack of KIR3DL1+ and HLA-Bw4-80Ile+ genotype, rescued KIR2DL1+ and HLA-C2/C2 patients from high relapse (p = 0.007). These findings support a role for NK cell graft-versus-leukemia activity modulated by NK cell receptor–ligand affinities in AHCT for AML.

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“…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 and clinical outcome of leukemia and certain types of solid tumors (9)(10)(11). There is a lack of clinical information on the role of KIR/HLA interactions in metastatic NSCLC (mNSCLC).…”

Section: Introductionmentioning

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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Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with solid tumors

Cited by 52 publications

References 40 publications

KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population

KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population

KIR and HLA Genotypes Predictive of Low-Affinity Interactions Are Associated with Lower Relapse in Autologous Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

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

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