Killer-cell immunoglobulin-like receptor genes and ligands and their role in hematologic malignancies

Varbanova, V.; Naumova, Elissaveta; Mihaylova, Anastasiya

doi:10.1007/s00262-016-1806-9

Cited by 26 publications

(27 citation statements)

References 120 publications

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“…An additional escape strategy used by cancer cells is based on the dominance of NK cell inhibitory signals. In several cancer cells, expression of MHC class I molecules binding to inhibitory KIR receptors (KIR2DL2/3, KIR3DL1, and KIR2DL1) results in switch off NK cell effector functions (37, 73–75). Moreover, high levels of non-classical antigens HLA-G (ligand of ILT-2 and KIRDL-4) and HLA-E (ligand of NKG2A/CD94) were found in tumor and serum of cancer patients and were considered independent markers of poor prognosis in various malignancies (76–79).…”

Section: Tumor Escape From Nk Cell-mediated Recognition and Killingmentioning

confidence: 99%

Role of Distinct Natural Killer Cell Subsets in Anticancer Response

et al. 2017

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Natural killer (NK) cells, the prototypic member of innate lymphoid cells, are important effectors of anticancer immune response. These cells can survey and control tumor initiation due to their capability to recognize and kill malignant cells and to regulate the adaptive immune response via cytokines and chemokines release. However, several studies have shown that tumor-infiltrating NK cells associated with advanced disease can have profound functional defects and display protumor activity. This evidence indicates that NK cell behavior undergoes crucial alterations during cancer progression. Moreover, a further level of complexity is due to the extensive heterogeneity and plasticity of these lymphocytes, implying that different NK cell subsets, endowed with specific phenotypic and functional features, may be involved and play distinct roles in the tumor context. Accordingly, many studies reported the enrichment of selective NK cell subsets within tumor tissue, whereas the underlying mechanisms are not fully elucidated. A malignant microenvironment can significantly impact NK cell activity, by recruiting specific subpopulations and/or influencing their developmental programming or the acquisition of a mature phenotype; in particular, neoplastic, stroma and immune cells, or tumor-derived factors take part in these processes. In this review, we will summarize and discuss the recently acquired knowledge on the possible contribution of distinct NK cell subsets in the control and/or progression of solid and hematological malignancies. Moreover, we will address emerging evidence regarding the role of different components of tumor microenvironment on shaping NK cell response.

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Section: Tumor Escape From Nk Cell-mediated Recognition and Killingmentioning

confidence: 99%

Role of Distinct Natural Killer Cell Subsets in Anticancer Response

et al. 2017

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“…The KIR gene family includes 14 loci (KIR2DL1, KIR2DL2/3, KIR2DL4, KIR2DL5A/B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1/S1, KIR3DL2, KIR3DL3 and two pseudogenes, KIR2DP1 and KIR3DP1) [31]as shown in Table 1. These loci are located on chromosome 19q13.4, which is known as the leukocyte receptor cluster (LRC); each haplotype has 9-15 KIR genes in a row [32].…”

Section: Genetics Of Kirsmentioning

confidence: 99%

“…KIRs are type I transmembrane glycoproteins expressed on the surface of NK cells, composed of two (2D) or three (3D) extracellular Ig-like domains and a cytoplasmic short (activating) or long (inhibitory) tail [31]. The length of the intracytoplasmic part determines the function; for example, receptors with long cytoplasmic tails with one or two ITIMs that bind to phosphatase SHP-1, 2 allow the transduction of inhibitory signals through its dephosphorylation.…”

Section: Kirs Subtypesmentioning

confidence: 99%

“…In contrast, receptors with short cytoplasmic tails possess a positively charged residue (lysine) in the transmembrane domain that enables it to associate with adaptor proteins including DAP12 and process the immunoreceptor tyrosine-based activation motifs (ITAMs) [29]. There is one exception: KIR2DL4, with a long cytoplasmic tail, binds to the activation motif of FcεRIγ and thus seems to transmit the activating signal [31].…”

Section: Kirs Subtypesmentioning

confidence: 99%

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Clinical Applications of Natural Killer Cells

Harada¹,

Teraishi²,

Ishii³

et al. 2017

Natural Killer Cells

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Natural killer (NK) cells are an essential component of the innate immune system, and they play a crucial role in immunity against malignancies. Recent advances in our understanding of NK cell biology have paved the way for new therapeutic strategies based on NK cells for the treatment of various cancers. In this section, we will focus on NK cell immunotherapy, including the enhancement of antibody-dependent cellular cytotoxicity, the manipulation of receptor-mediated activation, inclusion criteria based on killer cell immunoglobulin-like receptor (KIR) ligand mismatches, and adoptive immunotherapy with ex vivo expanded chimeric antigen receptor (CAR)-engineered or engager-modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack any recipient tissues based on allogeneic human leukocyte antigens (HLAs), suggesting that NK-mediated antitumor effects may be achieved without the risk of graft-versus-host disease (GvHD). Despite reports of clinical efficacy, the application of NK cell immunotherapy is limited. Developing strategies for manipulating NK cell products, host factors, and tumor targets are thus current subjects of diligent study. Research into the biology of NK cells has indicated that NK cell immunotherapy has the potential to become the forefront of cancer immunotherapy in the coming years.

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“…How NK cells may be relevant in hematologic malignancies, some of which are much more common in the elderly than in the young, is considered by Varbanova et al [2] who present a detailed critical review of the increasing evidence for the relevance of KIR and HLA class I ligand genetic background in the development of these diseases. Summarizing the current data, they conclude that two genetic profiles could be outlined in hemoblastosis which are associated either with higher levels of KIR-mediated inhibition or with a high level of KIR-mediated activation of NK cell function.…”

mentioning

confidence: 99%