The immune microenvironment confers resistance to MAPK pathway inhibitors through macrophage-derived TNFα

免疫微环境通过巨噬细胞衍生的 TNFα 产生对 MAPK 通路抑制剂的抵抗力

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作者:Michael P Smith #, Berta Sanchez-Laorden #, Kate O'Brien, Holly Brunton, Jennifer Ferguson, Helen Young, Nathalie Dhomen, Keith T Flaherty, Dennie T Frederick, Zachary A Cooper, Jennifer A Wargo, Richard Marais, Claudia Wellbrock

Significance

This study identifies the immune microenvironment as a source of resistance to MAPK pathway inhibitors through macrophage-derived TNFα, and reveals that in patients on treatment this source becomes reinforced. Inhibiting IκB kinase enhances the efficacy of MAPK pathway inhibitors, which identifies this approach as a potential novel strategy to improve targeted therapy in melanoma.

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