Human NK cell receptors/markers: A tool to analyze NK cell development, subsets and function

Montaldo, Elisa; Zotto, Genny Del; Chiesa, Mariella Della; Mingari, Maria Cristina; Moretta, Alessandro; Maria, Andrea De; Moretta, Lorenzo

doi:10.1002/cyto.a.22302

Cited by 181 publications

(166 citation statements)

References 111 publications

(129 reference statements)

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“…Among genes upregulated in IMtreated samples, we found those encoding constant and variable chains of the immunoglobulin family and genes encoding components of the NK pathway and NK-mediated lysis, such as NKG7 and GZMB. These findings correlated with the pathologic evidence in these specimens of B cells, which likely play a role in adaptive-specific immunity and in Fc receptor-dependent phagocytosis, and CD57-positive lymphoid cells, essentially consisting of finally differentiated, cytotoxic-competent NK cells (33,34). This strongly suggests that IM-induced alterations on tumor cells in turn trigger the activation of this innate response in DFSP/FS-DFSP, as already described in GIST (35)(36)(37).…”

Section: Discussionsupporting

confidence: 85%

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Stacchiotti¹,

Pantaleo²,

Negri³

et al. 2015

Clin Cancer Res

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Purpose: To report on imatinib mesylate (IM) in patients with metastatic dermatofibrosarcoma protuberans (DFSP)/fibrosarcomatous (FS)-DFSP and on the impact of the treatment on tumor biology.Experimental design: Ten consecutive patients treated with IM from 2007 to 2015 for a metastatic relapse from DFSP/FS-DFSP were identified. FISH analysis for COL1A1-PDGFB was performed. Two IM-treated and 4 na€ ve FS-DFSP were transcriptionally profiled by RNAseq on HiScanSQ platform. Differential gene expression was analyzed with edgeR (Bioconductor), followed by hierarchical clustering and Principal Component Analysis.Results: All cases featured fibrosarcomatous in the metastasis and retained the COL1A1-PDGFB. Best RECIST response was: 8 partial response, 1 stable disease, and 1 progressive disease. Median progression-free survival was 11 months. Five patients received surgery after IM and all relapsed. IM was restored in 4 patients with a new response. After IM, the most upregulated genes included those encoding for immunoglobulins and those affecting functions and differentiation of endothelial cells. Pathway enrichment analysis revealed upregulation in genes involved in antigen processing and presentation, natural killer-mediated cytotoxicity, and drug and xenobiotics metabolism. Conversely, a significant down-regulation of kinase signaling pathways was detected.Conclusions: All metastatic cases were fibrosarcomatous. Most patients responded to IM, but PFS was shorter than reported in published series which included both DFSP and FS-DFSP. All patients operated after IM had a relapse, suggesting that IM cannot eradicate metastatic cases and that the role of surgery is limited. Transcriptional profile of na€ ve and posttreatment samples pointed the contribution of immune infiltrates in sustaining the response to IM.

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Section: Discussionsupporting

confidence: 85%

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Stacchiotti¹,

Pantaleo²,

Negri³

et al. 2015

Clin Cancer Res

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“…Human NK cells are usually categorized into two main subsets: CD56 bright CD16 +/2 (CD56 bright ) and CD56 dim CD16 + (CD56 dim ) NK cells (8,9). CD56 bright NK cells are considered the precursors of CD56 dim NK cells and represent 5-15% of NK cells in blood (10,11).…”

Section: 1mentioning

confidence: 99%

“…CD56 dim NK cells constitutively express high levels of perforin and granzyme B, resulting in efficient lysis of target cells without prior stimulation (14). In contrast, CD56 bright NK cells express perforin but require preactivation to exert cytotoxicity (8,9,11).…”

Section: 1mentioning

confidence: 99%

“…Furthermore, like CD56 bright and CD56 dim NK cells, ltNK cells expressed the transcription factor EOMES (data not shown). The inhibitory receptor NKG2A, which is lost during NK cell differentiation (8,9), was expressed by 62% (mean) of ltNK cells, between the proportion of NKG2A + CD56 bright and NKG2A + CD56 dim NK cells (Fig. 2, Supplemental Fig.…”

Section: Phenotype Of Ltnk Cellsmentioning

confidence: 99%

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Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population

Lugthart

Melsen

Vervat

et al. 2016

The Journal of Immunology

122

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Knowledge of human NK cells is based primarily on conventional CD56bright and CD56dim NK cells from blood. However, most cellular immune interactions occur in lymphoid organs. Based on the coexpression of CD69 and CXCR6, we identified a third major NK cell subset in lymphoid tissues. This population represents 30–60% of NK cells in marrow, spleen, and lymph node but is absent from blood. CD69+CXCR6+ lymphoid tissue NK cells have an intermediate expression of CD56 and high expression of NKp46 and ICAM-1. In contrast to circulating NK cells, they have a bimodal expression of the activating receptor DNAX accessory molecule 1. CD69+CXCR6+ NK cells do not express the early markers c-kit and IL-7Rα, nor killer cell Ig-like receptors or other late-differentiation markers. After cytokine stimulation, CD69+CXCR6+ NK cells produce IFN-γ at levels comparable to CD56dim NK cells. They constitutively express perforin but require preactivation to express granzyme B and exert cytotoxicity. After hematopoietic stem cell transplantation, CD69+CXCR6+ lymphoid tissue NK cells do not exhibit the hyperexpansion observed for both conventional NK cell populations. CD69+CXCR6+ NK cells constitute a separate NK cell population with a distinct phenotype and function. The identification of this NK cell population in lymphoid tissues provides tools to further evaluate the cellular interactions and role of NK cells in human immunity.

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“…+ hematopoietic progenitor cells which can also give rise to T cells, B cells, and dendritic cells [54]. Particular transcription factors such as purine rich box-1 (PU.1), E26 transformation-specific (ETS-1), thymocyte selection-associated HMG box factor (TOX), the mammalian transcription factor E4 binding protein 4 (E4BP4), eomesodermin (Eomes), and T-box transcription factor (T-bet) are required for NK cell maturation stages [55][56][57][58].…”

Section: Nk Cells Develop From Cd34mentioning

confidence: 99%

Donor Natural Killer Cells and Their Therapeutic Potential in Allogeneic Hematopoietic Stem Cell Transplantation

Hu¹,

Liu²

2017

Natural Killer Cells

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Natural killer (NK) cells were first identified and named for their "natural" cytotoxicity to reject bone-marrow allografts in lethally irradiated mice. Different from T cells, NK cells require no prior sensitization or immunization to lyse transformed or virally infected target cells and are non-major histocompatibility complex (MHC)-restricted. However, recent progress in understanding of NK cells biology has proved that NK cells share some similar characteristics with T cells. During development, NK cells also undergo "education" according to "missing self" principle, thereby become mature and acquire effector function. The discovery that NK cells are able to "remember" prior certain stimulations indicates they may also contribute to adaptive immunity. After hematopoietic stem cell transplantation (HSCT), NK cells are the first donor-derived lymphogenous cells to reconstitute and alloreactivitiy of donor-derived NK cells have been shown to mediate graft-versus-leukemia (GvL) effect rather than to induce graft-versus-host disease (GvHD). These properties make donor-derived NK cells appealing for applications to benefit the outcome of HSCT. Here, we will review the improved understanding of NK cell biology, discuss characteristics of donor-derived NK cells which are associated with beneficial outcome of HSCT and explore novel methodologies that enhance the therapeutic effect of donor NK cells.

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Human NK cell receptors/markers: A tool to analyze NK cell development, subsets and function

Cited by 181 publications

References 111 publications

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population

Donor Natural Killer Cells and Their Therapeutic Potential in Allogeneic Hematopoietic Stem Cell Transplantation

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