Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Martínez‐Sánchez, María V.; Periago, Adela; Legáz, Isabel; Gimeno, Lourdes; Mrowiec, Anna; Montes-Barqueros, Natividad R.; Campillo, José A.; Bolarín, José Miguel; Bernardo, María Victoria; López-Álvarez, María R.; Gonzalez, Celia; García-Garay, María C; Muro, Manuel; Cabañas-Perianes, Valentín; Fuster, José Luís; García‐Alonso, Ana M.; Moraleda, José M.; Álvarez-López, María R.; Minguela, Alfredo

doi:10.1080/2162402x.2015.1093721

Cited by 19 publications

(32 citation statements)

References 55 publications

(66 reference statements)

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“…3A). Lower progression-free rates were observed for both HLA-C*16:01 (8.3%) and Genetic data from bladder cancer, OSC [23], and PCD [24] series coincides with a series used in previous studies aimed at describing the role of NK cell education in tumor immune surveillance. * HLA-I ligands for KIR2DS4 [21].…”

Section: 3supporting

confidence: 78%

“…The 10-yr progression-free rates were 89.5% for CIS + Ta, 82.1% for T1, and 42.9%, 33.3%, and 37.5% for T2/T4 after cystectomy, cystectomy + chemotherapy, and palliative, respectively. Genetic data for BC, OSC, and PCD patients coincide with a series of patients included in previous studies [22,24]. BC patients showed a significantly higher frequency of KIR2DL5 (66.7%, p c = 0.004) than HC (51.5%), OSC (56.7%), and PCD (54.9%) patients.…”

Section: Demographic Clinical and Treatment Detailssupporting

confidence: 77%

“…These NKcs are likely to be weak (C1C2 genotype) or not inhibited at all (C2C2 genotype) by their C1 ligand, meaning that they would efficiently control cancer progression. KIR2DL1 + L2 + L3 + / C1C1 + showed the most diverse repertoire of NKc subsets (KIR2DL1 + , KIR2DL2 + , and/or KIR2DL3 + ), with moderate expression of KIR2DL2/S2 receptors so that the double dose of C1C1 ligand would efficiently educate both KIR2DL2 + and KIR2DL3 + NKc subsets, which could efficiently control cancer progression [24]. A third genotype, KIR2DL1 + L2 + L3 À , associated with reduced PFS, is evident among KIR2DL5 À BC patients.…”

Section: Discussionmentioning

confidence: 99%

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Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

Guillamón

Gimeno

Server

et al. 2021

European Urology Oncology

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Section: 3supporting

confidence: 78%

Section: Demographic Clinical and Treatment Detailssupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

Guillamón

Gimeno

Server

et al. 2021

European Urology Oncology

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“…NKc education is also important in an autologous setting and contributes to immune surveillance against solid tumors (11). This is particularly relevant when transformed cells do not downregulate, but instead upregulate HLA expression, as has been reported in myelomas where the overexpression of HLA-I makes effective cancer immune surveillance highly dependent on multiple and diverse licensing interactions (12).…”

Section: Introductionmentioning

confidence: 98%

NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome

Guillamón

Martínez‐Sánchez

Gimeno

et al. 2018

Cancer Immunology Research

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Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro. Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A with their cognate HLA class-I ligands optimizes NKc functional competence. This work has evaluated the role of licensing interactions in NKc differentiation and the survival of cancer patients. We have analyzed KIR and KIR-ligand genes, and the expression of activating (CD16 and DNAM-1/CD226) and inhibitory (NKG2A and iKIRs) receptors on peripheral blood NKcs in 621 healthy controls and 249 solid cancer patients (80 melanoma, 80 bladder, and 89 ovarian). Licensing interactions upregulated the expression of activating CD226, reduced that of iKIR receptors, and shifted the CD226/iKIR receptor ratio on NKc membranes to activating receptors. A high tumor burden decreased CD226 expression, reduced the ratio of CD226/iKIR, and negatively affected patient survival. The progression-free survival (38.1 vs. 67.0 months, P < 0.002) and overall survival (56.3 vs. 99.6 months, P < 0.00001) were significantly shorter in patients with lower expression of CD226 on NKcs. Hence, transformed cells can downmodulate these licensing-driven receptor rearrangements as a specific mechanism to escape NKc immune surveillance. Our results suggest the importance of the CD226/ iKIR receptor ratio of NKcs induced by licensing interactions as critical determinants for solid cancer immune surveillance, and may provide predictive biomarkers for patient survival that may also improve the selection of donors for NKc immunotherapy. Cancer Immunol Res; 6(12); 1537-47. Ó2018 AACR. NKcs can also express up to 6 different activating KIR (aKIRs): KIR2DS1-5 and KIR3DS1. Only the interactions between KIR2DS1/HLA-C2 allotypes (15, 16), KIR2DS4/HLA-A Ã 1102, and to a limited number of HLA-C1/-C2 alleles and KIR3DS1 Ã 014/HLA-Bw4 (17-19) have been reported, although

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“…In addition, these variations are not restricted to activators on NK cells. Some studies had shown that NK cell impairment was associated with upregulated receptors expression such as NKG2A, KIR2DL1/L2/L3 [13][14][15]. In the liver, NK cells enrich remarkably, where the importance of cytotoxicity and antitumor immunomodulation induced by those cells is broadly recognized.…”

mentioning

confidence: 99%

Increased expression of activating receptors and up-regulated function of natural killer cells in peripheral blood of patients with HBV-related hepatocellular carcinoma

Pei

Yuan

Zhang

et al. 2020

Preprint

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BackgroundThis study aimed to investigate and identify the characteristics of peripheral natural killer (NK) cells of hepatocellular carcinoma (HCC) patients who infected with hepatitis B virus. MethodsFlow cytometry was utilized to identify the frequency and receptors of NK cells, in the meantime, to analyze the killing ability and cytotoxicity of NK cells of patients of which embraced 36 cases of HBVassociated HCC, 34 individuals who suffered in HBV-associated cirrhosis (LC) and 30 non-liver dysfunction healthy individuals as control (HC). ResultsCell counts for NK and CD56 dim NK were reduced in patients with HCC, however, there was no statistically significant. The count of CD56 bright NK cells in the HCC subpopulation was remarkably higher than the subset of the HC (P < 0.05). The counts of activated receptors of NKG2D/p30 were elevated in patients with HCC, as well as the NKp44 and the NKp46. There was no statistically meaningful difference of inhibitory receptor expressions such as CD158a/b on peripheral NK cells of patients with HCC and LC and those with HC (P > 0.05). Following an IL-12 stimulation, the production of INF-γ/-α of patients with HCC was less than those produced by HC (P < 0.05). However, killing activity and cytotoxicity, as the primary responsibilities of the natural killer cells, were upregulated in HCC individuals. HBV associated individuals were found lower counts and capability to produce cytokines of natural killer cells. Nevertheless, the killing capacity and cytotoxicity of NK cells were stronger than those of the HC group. This may be associated with the increased activating receptors expression of NK cells. ConclusionsThis study demonstrated that the activating receptors expression and the cytotoxicity of NK cells in the blood were independent predictors of development in HCC patients, and the recovery of NKG2D + CD56 dim NK cells could increase the prognostic value.

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Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Cited by 19 publications

References 55 publications

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome

Increased expression of activating receptors and up-regulated function of natural killer cells in peripheral blood of patients with HBV-related hepatocellular carcinoma

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