Characterization of tumor infiltrating Natural Killer cell subset

Levi, Itzhak; Amsalem, Hagai; Nissan, Aviram; Darash-Yahana, Merav; Peretz, Tamar; Mandelboim, Ofer; Rachmilewitz, Jacob

doi:10.18632/oncotarget.3453

Cited by 107 publications

(90 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, this also was demonstrated in PF from a patient with gastric cancer (60). One might hypothesize that the accumulation of CD56 bright NK cells in the peritoneum is the consequence of obstruction of the peritoneal lymphatic circulation, because this subpopulation is characteristic of secondary lymphoid organs.…”

Section: Cd56 Bright Nk Cells In Tissuesmentioning

confidence: 70%

“…However, the lack of information on the composition of NK cell subsets in the peritoneum of healthy donors makes a conclusion difficult. Nevertheless, it should be noted that PF from a patient with pancreatic cancer did not exhibit such an accumulation of CD56 bright cells; the CD56 dim subset was the major population (60). This discrepancy between cancer types may indicate that tumor-related factors are involved in the modulation of CD56 expression.…”

Section: Cd56 Bright Nk Cells In Tissuesmentioning

confidence: 91%

“…This discrepancy between cancer types may indicate that tumor-related factors are involved in the modulation of CD56 expression. In contrast, an accumulation of CD56 bright NK cells was also observed in the pleural fluid of patients with lung cancer (61), melanoma, or BC (60). In this context, it seems to be specific to the tumor, because noncancerous patients never presented such a high percentage of CD56 bright NK cells in comparison with the peripheral NK cell subpopulations (62).…”

Section: Cd56 Bright Nk Cells In Tissuesmentioning

confidence: 98%

See 2 more Smart Citations

Human CD56bright NK Cells: An Update

Michel

Poli

Cuapio

et al. 2016

The Journal of Immunology

315

273

View full text Add to dashboard Cite

Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56brightCD16−/dim NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56bright NK cells in health and disease and briefly discuss the current controversies surrounding them.

show abstract

Section: Cd56 Bright Nk Cells In Tissuesmentioning

confidence: 70%

Section: Cd56 Bright Nk Cells In Tissuesmentioning

confidence: 91%

Section: Cd56 Bright Nk Cells In Tissuesmentioning

confidence: 98%

See 1 more Smart Citation

Human CD56bright NK Cells: An Update

Michel

Poli

Cuapio

et al. 2016

The Journal of Immunology

315

273

View full text Add to dashboard Cite

show abstract

“…Expression levels were normalized to the vehicle control. detected in patients with non-small cell lung cancer, breast tumors, and colon tumors ( 33,34 ). The presence of VEGFAproducing NK cells is associated with a poor prognosis, showing that NK-cell-derived VEGFA plays a part in human disease.…”

Section: Y694mentioning

confidence: 99%

STAT5 Is a Key Regulator in NK Cells and Acts as a Molecular Switch from Tumor Surveillance to Tumor Promotion

et al. 2016

View full text Add to dashboard Cite

Natural killer (NK) cells are tightly regulated by the JAK-STAT signaling pathway and cannot survive in the absence of STAT5. We now report that STAT5-defi cient NK cells can be rescued by overexpression of BCL2. Our experiments defi ne STAT5 as a master regulator of NK-cell proliferation and lytic functions. Although NK cells are generally responsible for killing tumor cells, the rescued STAT5-defi cient NK cells promote tumor formation by producing enhanced levels of the angiogenic factor VEGFA. The importance of VEGFA produced by NK cells was verifi ed by experiments with a conditional knockout of VEGFA in NK cells. We show that STAT5 normally represses the transcription of VEGFA in NK cells, in both mice and humans. These fi ndings reveal that STAT5-directed therapies may have negative effects: In addition to impairing NK-cell-mediated tumor surveillance, they may even promote tumor growth by enhancing angiogenesis. SIGNIFICANCE:The importance of the immune system in effective cancer treatment is widely recognized. We show that the new signal interceptors targeting the JAK-STAT5 pathway may have dangerous side effects that must be taken into account in clinical trials: inhibiting JAK-STAT5 has the potential to promote tumor growth by enhancing NK-cell-mediated angiogenesis. Cancer Discov; 6(4); ©2016 AACR . Ni and Cerwenka, p. 347. See related commentary by INTRODUCTIONNatural killer (NK) cells are innate lymphocytes that develop from a common lymphoid progenitor in the bone marrow ( 1 ). They represent the fi rst line of defense against infected, stressed, and malignant cells. Recent evidence has assigned distinct features and functions to tissue-specifi c NK cells ( 2 ). NK cells have organ-specifi c properties, such as distinct profi les of receptor expression or cytokine production ( 3 ). Uterine NK cells secrete high levels of VEGFA and are involved in placental vascularization. The physiologic functions of other organ-specifi c NK-cell subsets are less well understood ( 4 ). STAT5 Is a Key Regulator in NK Cells and Acts as a Molecular Switch from Tumor Surveillance to Tumor PromotionDagmarAll aspects of NK-cell development are regulated by cytokines, their downstream signaling pathways, and transcriptional regulators. These include key cytokines such as IL2, IL12, IL15, IL18, and IL21 ( 5 ), most of which signal via the common γ chain ( 5 ) and activate the JAK-STAT pathway ( 6 ). JAK kinases (JAK1-3 and TYK2) bind to cytokine receptors and are activated by ligand/receptor binding. The activated kinase phosphorylates STAT transcription factors refs. 6,7 ).Consistent with its function as the major STAT protein downstream of IL7, IL2, and IL15, STAT5 is absolutely essential for conventional NK-cell development and survival; Stat5 Δ / Δ Ncr1-iCre Tg mice lack NK cells ( 8 ). It is also important for lymphoid cell development ( 9 ): STAT5 is constitutively active in a plethora of lymphoid malignancies ( 10 ). Recent studies have described somatic Stat5b mutations as active drivers of lymphoid mali...

show abstract

“…While the biological and clinical significance of their presence in early pregnancy is still under investigation, there are supporting evidences for both inhibitory and activating features, either in inhibition of anti-fetal immune response or in promotion of angiogenesis to support fetus implantation [26][32]. Recently it was shown that there was a significant enrichment of decidual-like NK cells within tumor infiltrating NK cell population which express pro-angiogenic factors and contribute to the tumor development [33]. Here we show that PILRα as a NK ligand, also activates dNK function by promoting killing and IFNγ secretion.…”

Section: Discussionmentioning

confidence: 99%

PILRα binds an unknown receptor expressed primarily on CD56bright and decidual-NK cells and activates NK cell functions

et al. 2016

Self Cite

View full text Add to dashboard Cite

Natural Killer (NK) cells are innate immune lymphocytes specializing in recognition and killing of tumors and pathogens, using an array of activating and inhibitory receptors. NK inhibition is mediated by a large repertoire of inhibitory receptors, whereas a limited number of activating NK cell receptors execute NK cell activation. The ligands recognized by the activating receptors are stress-induced, pathogen derived, tumor specific and even self ligands. However, the full spectrum of NK cell receptors and ligands that control NK cell activity remains uncharacterized. Here we demonstrate that Paired Ig-Like type 2 Receptor Alpha (PILRα), binds a distinct human NK cell sub-population present in the peripheral blood and also in the decidua. We further demonstrate that the interaction of NK cells with PILRα expressing targets lead to elevated IFNγ secretion and cytotoxicity. In conclusion, we present here a novel NK activating ligand which binds and activates an unknown NK receptor expressed on a unique NK cell subset.

show abstract

Characterization of tumor infiltrating Natural Killer cell subset

Cited by 107 publications

References 17 publications

Human CD56bright NK Cells: An Update

Human CD56bright NK Cells: An Update

STAT5 Is a Key Regulator in NK Cells and Acts as a Molecular Switch from Tumor Surveillance to Tumor Promotion

PILRα binds an unknown receptor expressed primarily on CD56bright and decidual-NK cells and activates NK cell functions

Contact Info

Product

Resources

About