EGR2 O-GlcNAcylation Orchestrates the Development of Protumoral Macrophages to Limit CD8+ T Cell Antitumor Responses.

Tumor associated macrophages (TAMs) exihibit a high capacity to take up glucose, however, how metabolic cues derived from glucose uptake rewire TAMs remains unclear. Here, we report that glucose metabolism-driven protein O-GlcNAcylation shapes the differentiation of protumoral TAMs, thereby accelerating tumor progression. We constructed O-GlcNAc transferase (OGT) conditional-deletion mice to examine MC38 tumor growth. Overall design: ATAC-seq on tumor-associated macrophages(TAMs) from mouse MC38 tumor, tumor-associated macrophages expressing or not the O-GlcNAc transferase(OGT), and CUT-tag-seq with early growth response gene(EGR2) on TAMs in MC38 tumor from Ogt-flox(WT) or Ogt-flox Lyz2-cre(KO) mice. ChIP-seq of EGR2 on TAMs in MC38 tumor from WT mice. RNA-seq of TAMs and scRNA-seq of CD45+ immune cells in MC38 tumor from Ogt-flox(WT) or Ogt-flox Lyz2-cre(KO) mice.