NK cell density in malignant skin tumours—a stereological study

Smolle, Josef; Soyer, H. Peter; Ehall, R; Stettner, Haro; Kerl, Helmut

doi:10.1111/j.1365-2133.1987.tb04901.x

Cited by 12 publications

(5 citation statements)

References 17 publications

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“…3B ). Our observation that there may be a lower abundance of NK cells in SCC corresponds to previous findings in which the NK density within SCC lesions was reported to be approximately 10-fold lower than in the germinal centres of normal human tonsils [22] . In Head and Neck SCC, NK-mediated antibody-dependent cellular cytotoxicity (ADCC) has been linked to the efficacy of anti-EGFR monoclonal antibody therapies [23] .…”

Section: Discussionsupporting

confidence: 91%

Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage

et al. 2014

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Squamous Cell Carcinoma (SCC) is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can develop from premalignant lesions including Intraepidermal Carcinoma (IEC). Notably, while SCC regression is rare, IEC typically regresses in response to immune modifying topical treatments, however the underlying immunological reasons for these differential responses remain unclear. This study aimed to define whether IEC and SCC are associated with distinct immune profiles. We investigated the immune cell infiltrate of photo-damaged skin, IEC, and SCC tissue using 10-colour flow cytometry following fresh lesion digest. We found that IEC lesions contain higher percentages of CD3+ T-cells than photo-damaged skin, however, the abundance of CD3−CD56+ Natural Killer (NK) cells, CD11c+HLA-DR+ conventional Dendritic Cells (cDC), BDCA-2+HLA-DR+ plasmacytoid DC (pDC), FoxP3+ Regulatory T-cells (T-reg), Vα24+Vβ11+ invariant NKT-cells, and γδ Tcells did not alter with disease stage. Within the total T-cell population, high percentages of CD4+ T-cells were associated with SCC, yet CD8+ T-cells were less abundant in SCC compared with IEC. Our study demonstrates that while IEC lesions contain a higher proportion of T-cells than SCC lesions in general, SCC lesions specifically display a lower abundance of CD8+ T-cells than IEC. We propose that differences in CD8+ T-cell abundance contribute critically to the different capacity of SCC and IEC to regress in response to immune modifying topical treatments. Our study also suggests that a high ratio of CD4+ T-cells to CD8+ T-cells may be a immunological diagnostic indicator of late-stage SCC development in immune-competent patients.

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Section: Discussionsupporting

confidence: 91%

Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage

et al. 2014

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“…While NK cells are highly relevant in the treatment of leukaemia, their role in the therapy of solid tumor is not yet fully exploited . Most solid tumors have very low levels of infiltration by NK cells . However, high levels of intra‐tumoral infiltration of NK cells in gastric, renal and squamous cell lung or oropharyngeal carcinoma have been shown to be associated with a favourable outcome .…”

Section: Introductionmentioning

confidence: 99%

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy

Tietze¹,

Angelova²,

Heppt³

et al. 2017

Experimental Dermatology

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The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 and CD56 NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 NK cells, whereas the baseline levels of CD56 NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 and CD56 NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 NK cells as well as normal baseline levels of CD56 NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 and CD56 NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.

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“…All these cells have many subsets based on their maturation, activation, expansion stages and are characterized by their own growth response to activating stimuli. For instance, NK cells are large granular lymphocytes of low cell density 44 . It is known, NK cells do not express cell-surface CD3.…”

Section: Resultsmentioning

confidence: 99%

Intracellular K+ and water content in human blood lymphocytes during transition from quiescence to proliferation

Marakhova

Yurinskaya

Aksenov

et al. 2019

Sci Rep

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Many evidence shows that K+ ions are required for cell proliferation, however, changes in intracellular K+ concentration during transition of cells from quiescence to cycling are insufficiently studied. Here, we show using flame emission assay that a long-term increase in cell K+ content per g cell protein is a mandatory factor for transition of quiescent human peripheral blood lymphocytes (PBL) to proliferation induced by phytohemagglutinin, phorbol ester with ionomycin, and anti-CD3 antibodies with interleukin-2 (IL-2). The long-term increase in K+ content is associated with IL-2-dependent stage of PBL activation and accompanies the growth of small lymphocytes and their transformation into blasts. Inhibition of PBL proliferation with drugs specific for different steps of G0/G1/S transit prevented both blast-transformation and an increase in K+ content per cell protein. Determination of the water content in cells by measuring the density of cells in the Percoll gradient showed that, unlike the K+ content, the concentration of K+ in cell water remains unchanged, since water and K+ change in parallel. Correlation of proliferation with high cell K+ and water content has been confirmed by the data obtained in comparative study of PBL and permanently cycling Jurkat cells. Our data suggest that K+ is important for successful proliferation as the main intracellular ion that participates in regulation of cell water content during cell transition from quiescence to proliferation. We concluded that high K+ content in cells and the associated high water content is a characteristic feature of proliferating cells.

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NK cell density in malignant skin tumours—a stereological study

Cited by 12 publications

References 17 publications

Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage

Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy

Intracellular K+ and water content in human blood lymphocytes during transition from quiescence to proliferation

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