Abstract
<p>USP6/Ewing sarcoma (ES) and NK cells participate in a paracrine feedforward loop mediated through IFNGR signaling in Ewing sarcoma cells. <b>A,</b> Diagram of proposed paracrine feedforward loop between USP6-expressing Ewing sarcoma cells and NK cells: (1) USP6/Ewing sarcoma cells activate NK cells; (2) activated NK cells secrete IFNγ, which feeds back on USP6/Ewing Sarcoma cells which have elevated surface levels of IFNGR; (3) IFNγ-inducible chemokines CXCL9/CXCL10 are synergistically induced in USP6-expressing cells, stimulating further NK cell recruitment, maturation, and activation. USP6/RD-ES were treated ± dox, in the absence or presence of NK-92 (0.1:1 E:T ratio). Samples were subjected to qRT-PCR (<i>n</i> ≥ 3; <b>B</b>), or intracellular flow cytometry to detect CXCL10 (<i>n</i> = 3; <b>C</b>). <b>D,</b> NK-92 were cocultured with USP6/RD-ES (either WT, or CRISPR-deleted IFNAR1 or IFNGR1 derivatives) at 0.1:1 ratio overnight, then subjected to qRT-PCR. CXCL9/CXCL10 mRNA levels were expressed relative to those in USP6/wild type (WT) RD-ES cells cocultured with NK-92 in the presence.</p>
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