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Fig. 6 | Journal for ImmunoTherapy of Cancer

Fig. 6

From: Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor

Fig. 6

NK histones promote cell clustering formation required for NK cells anti-MM activity. a: Cell clustering formation between CB-NK and MM-GFP and non-MM K562-GFP cells at 2.5 h and 24 h analyzing in parallel the impact of heparin (Hep) (see also Additional file 1: Figure S6A). b: 24 h cytotoxicity assays values obtained from co-cultures in a. c and d: Cell clustering formation at 2.5 h of co-culturing MM-GFP and non-MM K562-GFP cells with either CB-NK ctrl (siRNA ctrl) or CB-NK with knock-down of histones (siRNA Hist). Bar size indicates 100 μm. e and f: Impact of DNase and absence of Fetal bovine serum (FBS) in cell culture media on cell clustering formation (e) and CB-NK cytotoxicity (f) against MM and non-MM K562 cells. Heparin was added in parallel as control. g-j: Impact of recombinant H2AZ (g and h) and H4 (i and j), in the formation of cell clustering and in CB-NK cytotoxicity against MM and non-MM K562 cells. Cell clustering analysis was measured at 2.5 h (g and i) and cytotoxicity at 24 h (h and j). See also Additional file 1: Figure S6B. k-o: CD138 impact on histones activity. k-l: CD138 expression in MM and K562 cells after Heparinase III treatment for 1-2 h (k) and after CD138 knock-down with siRNAs (l). m. Tumor cells ctrl, after Heparinase III treatment (HSPG-) and after CD138 knock-down (CD138) were co-cultured with CB-NK adding exogenous H2AZ or H4 and cell clustering formation was evaluated at 2 h (n) and cytotoxicity at 6 h (o) (See also Additional file 1: Figure S6C). *p < 0.05. ** p < 0.001

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