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Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1

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Academic year: 2021

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Fig. 1 SPHK1 expression inversely correlates with survival after ICI therapy. a SPHK1 expression in human nevi (n = 17) compared to primary (P) melanoma (n = 45), and in primary melanoma (n = 25) compared to metastatic (M) melanoma (n = 44) based on the On
Fig. 2 SK1 downregulation increases the CD8 + /Treg ratio and reduces tumor growth. a SK1 enzymatic activity was measured in Yumm cells transfected with a control shRNA (shCtrl, black column) or two SK1-targeted shRNA (white and gray columns) (means ± SEM
Fig. 3 SK1 silencing reduces Treg accumulation in tumors. Control shRNA (shCtrl; black points) or SK1-targeted shRNA (shSK1(1); white points) Yumm melanoma cells were injected intradermally in C57BL/6 mice, and TIL content was analyzed by fl ow cytometry on
Fig. 4 SK1 inhibition enhances the ef fi cacy of anti-CTLA-4 or anti-PD-1 therapy. Control shRNA (shCtrl) or SK1-targeted shRNA (shSK1(1)) Yumm cells were injected on day 0, and then mice were treated with isotype (iso) control antibody (black lines; shCtrl
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