Mature Cytotoxic CD56bright/CD16<i>+</i>Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

Messaoudene, Meriem; Fregni, Giulia; Fourmentraux-Neves, Emmanuelle; Chanal, J.; Maubec, Ève; Mazouz-Dorval, Sarra; Couturaud, Benoît; Girod, Angélique; Sastre-Garau, Xavier; Albert, Sébastien; Guédon, C.; Deschamps, Lydia; Mitilian, Délphine; Cremer, Isabelle; Jacquelot, Nicolas; Rusakiewicz, Sylvie; Zitvogel, Laurence; Avril, Marie-Françoise; Caignard, Anne

doi:10.1158/0008-5472.can-13-1303

Cited by 83 publications

(74 citation statements)

References 48 publications

(37 reference statements)

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“…23 However, we also showed that metastatic lymph nodes contained NK subset CD56 bright CD16 C endowed with high lytic potential following activation by cytokines. 26 Depending of the disease stage localized or metastatic, lymph node NK cells may display different functions likely reflecting their recruitment from the tumor or their local activation.…”

Section: Discussionmentioning

confidence: 99%

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

et al. 2016

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Given the NK cell-based immunosurveillance of melanoma, we investigated the prognostic value of NKp46 transcript and NKp30 isoform (NKp30A, NKp30B and NKp30C) profiling in blood of 187 melanoma patients including 13 long survivors (LS), metastatic patients that have controlled the disease. Compared to healthy volunteers (HV), patients had reduced amounts of transcripts of the three NKp30 isoforms (NKp30 A, B and C) but similar ratios between NKp30 isoforms (DAB, DAC, DBC). Stratification of patients according to disease stage showed higher NKp30C and lower NKp46 transcripts in stage IV patients. Furthermore, patients with previous history of conventional chemotherapy displayed reduced NKp30A transcripts. The expression levels of NKp30 isoforms failed to predict survival from sampling of patients, while NKp46 expression predicted melanoma outcome. LS patients displayed elevated NKp30A levels, accordingly high DAB and DBC ratios, and a unique pattern of rare allelic variants of NKp30 SNPs. Moreover, NK cells from LS displayed correlated NKp30/NKp46 membrane expression, high spontaneous and NKp30-or NKp46-triggered degranulation. These data outline the impact of NKp30 and NKp46 transcripts on melanoma evolution and identify unique genetic features of NKp30 associated with higher NK activation in rare LS melanoma patients that control a metastatic disease.

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Section: Discussionmentioning

confidence: 99%

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

et al. 2016

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“…In the context of metastatic melanoma, two recent publications with complementary results reported the presence of CD56 bright NK cells with activated phenotype in tumor-infiltrating LNs (27,76). Interestingly, the CD56 dim subset was dominant in metastatic LNs (M-LNs) of all patients tested (CD56 dim : 55.52 6 21.5% versus CD56 bright : 44.5 6 21.5%), whereas the CD56 bright subset prevailed in tumor-free LNs, as observed in healthy individuals (27).…”

Section: Phenotypes Of Cd56 Bright Nk Cells In Disease Statesmentioning

confidence: 99%

“…It was noted that M-LNs contained NK cells with increased activation profiles: CD56 dim and CD56 bright subsets displayed elevated surface expression of CD16, CD57, CD69, CCR7, NKG2D, DNAM-1, NCR, and KIRs. The work of Messaoudene et al (76) further focused on the CD56…”

Section: Phenotypes Of Cd56 Bright Nk Cells In Disease Statesmentioning

confidence: 99%

Human CD56bright NK Cells: An Update

Michel

Poli

Cuapio

et al. 2016

The Journal of Immunology

305

273

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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.

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“…Previous studies have shown no differences in NKG2D expression between peripheral blood mononuclear cells (PBMCs) and LN NK cells in melanoma patients and healthy individuals. [33][34][35][36] However, these studies did not examine the NKG2D expression in tumor infiltrating NK cells. We observed significantly lower NKG2D expression in the intratumoral NK cells, but no difference in the splenic population, between naive and tumorbearing mice.…”

Section: Cd11bmentioning

confidence: 99%

Intratumoral natural killer cells show reduced effector and cytolytic properties and control the differentiation of effector Th1 cells

et al. 2016

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Natural killer (NK) cells are known to have effector and cytolytic properties to kill virus infected or tumor cells spontaneously. Due to these properties, NK cells have been used as an adoptive cellular therapy to control tumor growth in various clinical trials but have shown limited clinical benefits. This indicates that our knowledge about phenotypic and functional differences in NK cells within the tumor microenvironment and secondary lymphoid tissues is incomplete. In this work, we report that B16F10 cellinduced melanoma recruits the CD11b C CD27C subset of NK cells at a very early stage during tumor progression. These intratumoral NK cells showed increased expression of CD69, reduced inhibitory receptor KLRG1, and decreased proliferative ability. As compared to splenic NK cells, intratumoral NK cells showed decreased expression of activating receptors NKG2D, Ly49D and Ly49H; increased inhibitory receptors, NKG2A and Ly49A; decreased cytokines IFNg and GM-CSF; decreased cytokine receptors IL-21R, IL-6Ra, and CD122 expression. Depletion of NK cells led to decrease peripheral as well as intratumoral effector CD4 C T-bet C cells (Th1), and increased tumor growth. Furthermore, purified NK cells showed increased differentiation of Th1 cells in an IFNg-dependent manner. Anti-NKG2D in the culture promoted differentiation of effector Th1 cells. Collectively, these observations suggest that intratumoral NK cells possess several inhibitory functions that can be partly reversed by signaling through the NKG2D receptor or by cytokine stimulation, which then leads to increased differentiation of effector Th1 cells.

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Mature Cytotoxic CD56bright/CD16+Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

Cited by 83 publications

References 48 publications

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

Human CD56bright NK Cells: An Update

Intratumoral natural killer cells show reduced effector and cytolytic properties and control the differentiation of effector Th1 cells

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