Tyrosine kinase pathways modulate tumor susceptibility to natural killer cells

Bellucci, Roberto; Nguyen, Hong-Nam; Martin, Allison; Heinrichs, Stefan; Schinzel, Anna C.; Hahn, William C.; Ritz, Jérôme

doi:10.1172/jci58457

Cited by 33 publications

(46 citation statements)

References 45 publications

(48 reference statements)

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“…The cis-platinum-resistant A2780cis cells are less accessible for NK-cell mediated killing. This finding is in agreement with a recent report by Bellucci et al (26). Using a lentiviral shRNA library targeting >1,000 human genes they identified 83 genes that promote target cell resistance to human NK-cell-mediated killing (26).…”

Section: Discussionsupporting

confidence: 91%

“…Using a lentiviral shRNA library targeting >1,000 human genes they identified 83 genes that promote target cell resistance to human NK-cell-mediated killing (26). Many of the genes identified in this genetic screen belong to common signalling pathways including members of the AKT/PI3K-pathway such as PIK3CA and PIK3CB (26).…”

Section: Discussionmentioning

confidence: 99%

“…Our results revealed that the cells with an increase in phosphorylated AKT/activated PI3K/AKT pathway have a higher MICA/B expression. Recently Bellucci et al demonstrated that treatment of tumour cells with JAK inhibitors increased their susceptibility to NK-cell mediated killing (26). The authors concluded that common signalling pathways can regulate susceptibility of human tumour cells to killing by immunologic effector cells and that small molecule inhibitors of these kinases may have important immunologic effects in vivo (26).…”

Section: Discussionmentioning

confidence: 99%

“…Recently Bellucci et al demonstrated that treatment of tumour cells with JAK inhibitors increased their susceptibility to NK-cell mediated killing (26). The authors concluded that common signalling pathways can regulate susceptibility of human tumour cells to killing by immunologic effector cells and that small molecule inhibitors of these kinases may have important immunologic effects in vivo (26). Whether in analogy inhibition of PI3K/ AKT pathway renders the platinum-resistant A2780cis cells accessible for NK-cell mediated killing must be evaluated in further studies.…”

Section: Discussionmentioning

confidence: 99%

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Immune escape of AKT overexpressing ovarian cancer cells

Hahne

Meyer

Gambaryan

et al. 2013

International Journal of Oncology

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Abstract. Platinum-resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. As survival is strongly influenced by immunological parameters, immunotherapeutic strategies appear promising. Therefore a better understanding of the interaction between ovarian tumour cells and cells of the immune system is a necessary prerequisite. In the present study we aimed to enlighten the interactions between platinum resistant and platinum sensitive ovarian cancer cells and natural-killer (NK)-cells. Modified FATAL assay was used for determining the killing efficiency of NK-cells for the parental A2780 cells and the cis-platinum resistant A2780cis human ovarian cancer cells. Expression of pro-and anti-apoptotic genes as well as ligands involved in NK-cell receptor recognition were analysed by RT-PCR and flow cytometric analysis. The efficiency of NK mediated cell lysis differs between A2780 cells and the cis-platinum-resistant A2780cis cells. A2780cis cells are less accessible for NK-cell mediated killing. Based on this observation we characterized the molecular basis for resistance mechanisms. Besides an increase in anti-apoptotic genes (especially CIAP-1 and -2) that probably render A2780cis cells more resistant against apoptosis an increased amount of soluble MICA/B seems to be responsible for the lower killing rate of platinum-resistant A2780cis cells compared to their parental A2780 cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Immune escape of AKT overexpressing ovarian cancer cells

Hahne

Meyer

Gambaryan

et al. 2013

International Journal of Oncology

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“…Our data are also of importance when considering a recent paper showing that JAK inhibitors increase susceptibility of tumor cells to NK cellmediated killing. 8 However, in this report the authors only focused at JAK inhibitory effects on the tumor cell side, whereas the impact of JAK inhibition on the immune-cell side also has to be taken into account, as systemic JAK inhibition may counteract the sensitizing effects on the tumor cell level by impairing NK cell function. Moreover, in the context of allogeneic stem cell transplantation, where ruxolitinib has recently been suggested as a potential therapeutic option for the therapy of steroid-refractory GvHD, 9 the results might also be considered because NK cells are critical for the GvL effect.…”

mentioning

confidence: 99%