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. 2023 Jan 23;220(4):e20220686. doi: 10.1084/jem.20220686

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© 2023 Sun et al.

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Figure 5. — STAT3 transcriptionally regulates T_ex cell differentiation. (A) Venn diagram of pSTAT3-binding peaks in IL-6–, IL-10–, and IL-21–stimulated CD8⁺ T cells across the whole mouse genome (mm10). (B) Genetic feature distribution (upper panel) or distribution relative to TSS (bottom panel) of pSTAT3-binding peaks in CD8⁺ T cells. (C) Venn diagrams of pSTAT3-binding genes and DEGs in WT or Stat3^−/− CD8⁺ OT-I TILs. (D) Venn diagrams of STAT3-regulated genes and DEGs in T_ex^term or T_ex^prog TILs (GEO accession no. GSE114631). (E) Representative STAT3-regulated feature genes of T_ex^term (left panel) or T_ex^prog (right panel) cells. (F) UMAP plots identifying tumor-infiltrating memory-like and cytolytic CD8⁺ T cell clusters from human head and neck cancer (left panel) or melanoma (right panel) patient (GEO accession nos. GSE103322 and GSE120575). (G) Average expression of STAT3-induced (left panel) or -suppressed (right panel) signature gene clusters in memory-like or cytolytic tumor-infiltrating CD8⁺ T cells. STAT3-induced or -suppressed signature genes are listed in Table S3. (H) pSTAT3 ChIP-seq tracks aligned with RNA-seq tracks of WT and Stat3^−/− CD8⁺ TILs, and ATAC-seq tracks of T_ex^prog or T_ex^term cells at the specific gene loci (GEO accession no. GSE123236). (I) mRNA levels of specific genes in in vitro activated WT and Stat3^−/− CD8⁺ T cells with the stimulation of IL-10 for 2 d or not. Data are representative of three (I) independent experiments. Data are shown as mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by unpaired two-tailed Student’s t test (G and I).