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Updated: Oct 13, 2026

Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
A druggable chromatin vulnerability in suppressive neutrophils restores antitumor immunity
Abstract:
Many cancers evade immunity by converting neutrophils into polymorphonuclear myeloid - derived suppressor cells (PMN-MDSCs), but the chromatin mechanisms that maintain this pathological state remain unclear. Here we show that tumor-induced suppressive neutrophils depend on mSWI/SNF chromatin remodeling. Two orally bioavailable mSWI/SNF ATPase antagonists, a degrader and a catalytic inhibitor, produced immune-dependent tumor control across syngeneic models, including tumors resistant to PD-1 blockade, and enhanced checkpoint therapy without overt toxicity. Treatment rapidly depleted intratumoral PMN-MDSCs, restored functional CD8 + T cells, and blocked tumor explant-induced expansion and suppressive activity of mouse and human PMN-MDSCs. mSWI/SNF antagonism collapsed chromatin accessibility and PU.1/C/EBPβ occupancy at regulatory elements that sustain PMN-MDSC identity. Thus, suppressive neutrophils harbor a druggable chromatin vulnerability that can be exploited to restore cancer immunity.
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