Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid

Lennicke, Claudia; Rahn, Jette; Bukur, Jürgen; Hochgräfe, Falko; Wessjohann, Ludger A.; Lichtenfels, Rudolf; Seliger, Barbara

doi:10.1080/2162402x.2016.1259049

Cited by 20 publications

(18 citation statements)

References 69 publications

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“…In fact, major histocompatibility-I (MHC-I) present tumor antigens to CD8 + T cells to activate their cytotoxic activities, which is also affected by methylselenol in cancer cells. In particular, this selenium metabolite was shown to alter redox metabolism in melanoma cells and lead to increased levels of MHC-I cell surface antigens [ 168 ]. This study showed that the actions of methylselenol mimic IFNγ signaling by also upregulating members of IFNγ responsive genes.…”

Section: Selenium and Its Effects On A Shift Toward Anti-cancer Immentioning

confidence: 99%

Selenium, Selenoproteins, and Immunity

2018

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Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

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Section: Selenium and Its Effects On A Shift Toward Anti-cancer Immentioning

confidence: 99%

Selenium, Selenoproteins, and Immunity

2018

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“…In one study, Se-methyl-selenocysteine was more effective and dose-potent than seleno-l- methionine or sodium selenite in reducing cytotoxic chemotherapy-related mortality and augmenting its anticancer activity [ 6 ]. This may relate to the in vivo ability of Se-methyl-selenocysteine to directly generate methylselenol, a compound that is considered the active moiety for the observed effects of Se compounds in cancer cells [ 23 , 24 , 25 , 26 , 27 ]. In preclinical models Se-methyl-selenocysteine dosed at 0.2 mg/mouse/day optimises the mechanisms that mediate protection of normal tissues while enhancing tumour cytotoxicity [ 5 , 6 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells

Lobb

Jacobson

Cursons

et al. 2018

IJMS

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Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro. We specifically investigated its effects on endoplasmic reticulum stress induction, intracellular glutathione concentration, DNA damage and viability of peripheral blood mononuclear cells and THP1 monocytic leukaemia cells in response to radiation, cytosine arabinoside or doxorubicin chemotherapy. MSA, at lower concentrations, induced protective responses in normal cells but cytotoxic effects in malignant cells, alone and in conjunction with chemotherapy or radiation. However, in normal cells higher concentrations of MSA were directly toxic and increased the cytotoxicity of radiation but not chemotherapy. In malignant cells higher MSA concentrations were generally more effective in combination with cancer treatments. Thus, optimal MSA concentrations differed between normal and malignant cells and treatments. This work supports clinical reports that selenium can significantly reduce dose-limiting toxicities of anticancer therapies and potentially improve efficacy of anticancer treatments. The optimal selenium compound and dose is not yet determined.

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“…To examine the tumor surveillance capacity in the mouse model of XLN, we used syngeneic B16 melanoma cells, which have low expression of MHC class I molecules ( 45 ). We first examined the NK cell response to B16 melanoma cells in vitro after a 4-hour coculture.…”

Section: Resultsmentioning

confidence: 99%

Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells

Kritikou¹,

Oliveira²,

Record³

et al. 2021

JCI Insight

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X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich Syndrome protein (WASp). XLN patients have reduced numbers of cytotoxic cells in peripheral blood, however, their capacity to kill tumor cells remains to be determined. Here, we examined NK and T cells from two XLN patients harboring the activating WASp L270P mutation. XLN patient NK and T cells had increased Granzyme B content and elevated degranulation and IFNγ production when compared to healthy control cells. Murine WASp L272P NK and T cells formed stable synapses with YAC-1 tumor cells and anti-CD3/CD28 coated beads, respectively. WASp L272P T cells mice had normal degranulation and cytokine response whereas WASp L272P NK cells showed an enhanced response. Imaging experiments revealed that while WASp L272P CD8 T cells had increased accumulation of actin upon TCR activation, WASp L272P NK cells had normal actin accumulation at lytic synapses triggered through NKp46 signaling but had impaired response to LFA-1 engagement. When compared to WT mice, WASp L272P mice showed reduced growth of B16 melanoma and increased capacity to reject MHC class I-deficient cells. Together, our data suggests that cytotoxic cells with constitutively active WASp have an increased capacity to respond to and kill tumor cells.

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Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid

Cited by 20 publications

References 69 publications

Selenium, Selenoproteins, and Immunity

Selenium, Selenoproteins, and Immunity

The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells

Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells

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