Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

Carlsten, Mattias; Bc, Baumann; Simonsson, Moa; Jädersten, Martin; Forsblom, AM; Hammarstedt, Christina; Bryceson, Yenan T.; Hg, Ljunggren; Hellström‐Lindberg, Eva; Malmberg, Karl‐Johan

doi:10.1038/leu.2010.149

Cited by 87 publications

(90 citation statements)

References 42 publications

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“…DNAM-1 is involved in adhesion and immune synapse formation and was shown to play an important role in the control of cytotoxicity (44)(45)(46)(47). A bimodal expression pattern for DNAM-1 on human NK cells was only reported in bone marrow of myelodysplastic syndrome patients and in liver (41,48). The high surface expression intensity of the activating NK cell receptor NKp46 on ltNK cells is in line with the description of NKp46 bright NK cells in lymph node and spleen (20).…”

Section: Cd49asupporting

confidence: 48%

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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Section: Cd49asupporting

confidence: 48%

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

Lugthart

Melsen

Vervat

et al. 2016

The Journal of Immunology

122

View full text Add to dashboard Cite

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“…[12][13][14][15] In this context, it has been shown that sera derived from human AML patients may haematologica 2015; 100:e44 14 This effect was not detectable under our experimental condition, most likely due to the use of a trans-well system in which microvescicles cannot diffuse from upper to lower chambers containing cell precursors. Notably, previous reports regarding inhibitory AML-mediated effect focused on PB mature NK cells, and not on differentiating NK-cell precursors, which may display a different susceptibility to AML-derived inhibitory factors.…”

Section: Letters To the Editormentioning

confidence: 67%

IL-1 -releasing human acute myeloid leukemia blasts modulate natural killer cell differentiation from CD34+ precursors

et al. 2014

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“…First, we showed that breast tumor cells alter NK cell functions through the modulation of their surface receptors, a mechanism observed in several other malignancies (28,29,(44)(45)(46)(47). These alterations are associated with invasive characteristics and a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity

Mamessier¹,

Sylvain²,

Thibult³

et al. 2011

J. Clin. Invest.

539

494

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NK cells are a major component of the antitumor immune response and are involved in controlling tumor progression and metastases in animal models. Here, we show that dysfunction of these cells accompanies human breast tumor progression. We characterized human peripheral blood NK (p-NK) cells and malignant mammary tumor-infiltrating NK (Ti-NK) cells from patients with noninvasive and invasive breast cancers. NK cells isolated from the peripheral blood of healthy donors and normal breast tissue were used as controls. With disease progression, we found that expression of activating NK cell receptors (such as NKp30, NKG2D, DNAM-1, and CD16) decreased while expression of inhibitory receptors (such as NKG2A) increased and that this correlated with decreased NK cell function, most notably cytotoxicity. Importantly, Ti-NK cells had more pronounced impairment of their cytotoxic potential than p-NK cells. We also identified several stroma-derived factors, including TGF-β1, involved in tumor-induced reduction of normal NK cell function. Our data therefore show that breast tumor progression involves NK cell dysfunction and that breast tumors model their environment to evade NK cell antitumor immunity. This highlights the importance of developing future therapies able to restore NK cell cytotoxicity to limit/prevent tumor escape from antitumor immunity. IntroductionBreast cancer (BC) is the primary cause of cancer deaths in women. The main cause of this mortality is the metastatic spread to other organs (1). Metastasis occurs when tumor cells acquire invasive features (2) and the ability to escape from antitumor immunity (3, 4). Defects in antitumor immunity may also facilitate BC occurrence. Indeed, mice deficient in IFN-γ production spontaneously develop mammary tumors (5). Breast tumor cells transplanted into NOD/SCID mice (which lack adaptive immunity) form noninvasive tumors, whereas the same cells transplanted into NOD/SCID/γ-c null mice (no adaptive immunity and no NK cells) form invasive tumors that metastasize rapidly (6). This effect is strictly dependent on NK cells (7). Similarly, in a highly metastatic model, BC metastasized to the lung only after elimination of NK cells by Tregs (8).Advanced BC patients show defects in antitumor immunity, such as alterations of DC maturation (9) and an increase in Treg infiltrates (10). Major impairment of peripheral blood NK cell maturation and cytotoxic functions has also been reported in metastatic BC (11). Several gene expression profiling studies have shown that a better outcome is associated with a strong cytotoxic infiltrate containing NK cells (12)(13)(14)(15). These data suggest that BC progression is linked to antitumor immunity efficiency and particularly to NK cells. However, the precise relationships between NK cells and BC progression in humans have not been studied so far.

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Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

Cited by 87 publications

References 42 publications

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

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

IL-1 -releasing human acute myeloid leukemia blasts modulate natural killer cell differentiation from CD34+ precursors

Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity

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