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Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Zhao, Fei ; Evans, Kathy ; Xiao, Christine ; DeVito, Nicholas ; Theivanthiran, Balamayooran ; Holtzhausen, Alisha ; Siska, Peter J. ; Blobe, Gerard C. ; Hanks, Brent A.



Abstract

Although anti-PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the development of these mechanisms of resistance to checkpoint inhibitors remains unclear. We demonstrated that pharmacologic inhibition of the TGF beta signaling ...

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