Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells

Morandi, Fabio; Ferretti, Elisa; Castriconi, Roberta; Dondero, Alessandra; Petretto, Andrea; Bottino, Cristina; Pistoia, Vito

doi:10.1182/blood-2011-05-352393

Cited by 66 publications

(38 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed that in PBMC from patients with ATC, CXCR3 is predominantly expressed on CD56 bright NK cells compared with CD56 dim NK cells. This distribution of CXCR3 on NK cells has previously been described in healthy individuals and in patients with hepatitis C (41,42). We also found that the percentage of CXCR3-positive cells in FNA was higher in the CD56 bright NK cell population than in the CD56 dim NK cell population, indicating that the CD56 bright NK cells may have been preferentially recruited to the tumor possibly explaining the skewed ratio of CD56 dim NK cells.…”

Section: Discussionsupporting

confidence: 58%

Human Anaplastic Thyroid Carcinoma Cells Are Sensitive to NK Cell–Mediated Lysis via ULBP2/5/6 and Chemoattract NK Cells

Wennerberg

Pfefferle

Ekblad

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.Experimental Design: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.Results: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.Conclusions: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy. Clin Cancer Res; 20(22); 5733-44. Ó2014 AACR.

show abstract

Section: Discussionsupporting

confidence: 58%

Human Anaplastic Thyroid Carcinoma Cells Are Sensitive to NK Cell–Mediated Lysis via ULBP2/5/6 and Chemoattract NK Cells

Wennerberg

Pfefferle

Ekblad

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…One reason for this might be a different INAVA expression threshold required for distinct immunological outcomes. Expression/function threshold differences have been observed for various molecules (54,55).…”

Section: Discussionmentioning

confidence: 99%

An inflammatory bowel disease–risk variant in INAVA decreases pattern recognition receptor–induced outcomes

Yan¹,

Hedl²,

Abraham³

2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

“…This hypothesis is supported by the immunosuppressive properties of HLA-G, which act on all the cells involved in the immune response. In addition, sHLA-G downregulates CXCR3 levels on peripheral blood and tonsil CD56 cells [112]. This dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs antiviral responses in vivo, including the antiviral response to herpes simplex virus 1 infection [113].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Properties of HLA-G in Infectious Diseases

Amiot

Samson

2014

Journal of Immunology Research

View full text Add to dashboard Cite

HLA-G is a nonclassical major histocompatibility complex molecule first described at the maternal-fetal interface, on extravillous cytotrophoblasts. Its expression is restricted to some tissues in normal conditions but increases strongly in pathological conditions. The expression of this molecule has been studied in detail in cancers and is now also beginning to be described in infectious diseases. The relevance of studies on HLA-G expression lies in the well known inhibitory effect of this molecule on all cell types involved in innate and adaptive immunity, favoring escape from immune control. In this review, we summarize the features of HLA-G expression by type of infections (i.e, bacterial, viral, or parasitic) detailing the state of knowledge for each pathogenic agent. The polymorphism, the interference of viral proteins with HLA-G intracellular trafficking, and various cytokines have been described to modulate HLA-G expression during infections. We also discuss the cellular source of HLA-G, according to the type of infection and the potential role of HLA-G. New therapeutic approaches based on synthetic HLA-G-derived proteins or antibodies are emerging in mouse models of cancer or transplantation, and these new therapeutic tools may eventually prove useful for the treatment of infectious diseases.

show abstract

Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells

Cited by 66 publications

References 51 publications

Human Anaplastic Thyroid Carcinoma Cells Are Sensitive to NK Cell–Mediated Lysis via ULBP2/5/6 and Chemoattract NK Cells

Human Anaplastic Thyroid Carcinoma Cells Are Sensitive to NK Cell–Mediated Lysis via ULBP2/5/6 and Chemoattract NK Cells

An inflammatory bowel disease–risk variant in INAVA decreases pattern recognition receptor–induced outcomes

Immunomodulatory Properties of HLA-G in Infectious Diseases

Contact Info

Product

Resources

About