Extended Data Fig. 11: ho22R and hoGCSFR epigenetically rewire TILs in A375 xenograft tumour model.

a,b, Male NSG mice bearing A375 tumours e received an i.v. adoptive transfer of 3 × 10⁶ CD3⁺ NY-ESO-1 TCR-T cells on Day 6, followed by i.p. administration of MSA-hoIL2 every other day (n = 5 animals). a, Tumour growth curves. b, Survival curves. Indicated are the numbers of tumour-free mice per total number of mice. c, The experimental timeline for Fig. 6(h–n) and Extended Data Fig. 11d–h. Female NSG mice bearing A375 melanoma received an i.v. adoptive transfer of 3 × 10⁶ CD3⁺ NY-ESO-1 TCR-T cells on day 10, followed by i.p. administration of MSA-hoIL2 every other day. On day 21, the tumours were analysed by flow cytometry (n = 5 animals). On day 22, TCR-T cells in tumours were sorted for ATAC-seq analysis (n = 3 biological independent samples). d, MFI of PD-1, LAG−3, and TIM-3 among EGFR⁺CD8⁺ TCR-T cells in tumours (n = 5 animals). e, Principal component analysis (PCA). f, Proportions of differential or non-significant chromatin regions. g, KEGG pathway enrichment was performed on accessible promoter regions (TSS ± 1 kb) using one-tailed hypergeometric tests, with FDR-adjusted q values (Benjamini-Hochberg). h, Genes underlying the enrichment for the “KEGG cytokine-cytokine receptor interaction” term (differential chromatin regions within transcription start sites +/−1 kb of known genes). i–m, NT, ho22R, and ho22R (BACH2 knockout) CD3⁺ human T cells were restimulated with soluble CD3 antibodies (1 μg/mL) in the presence of MSA-hoIL2 (200 nM) for 48 h (n = 4). Cells were then collected for quantitative PCR and flow cytometry analysis. i, Relative expression of BACH2 (n = 4 biologically independent samples). j–m, MFI of CD62L (j), CD44 (k), TCF-1 (l), FOXO1 (m). All data represent mean ± s.e.m. and are analysed by one-way ANOVA (d, j–m), or two-way (a) ANOVA with Tukey’s post-test, or log-rank (Mantel-Cox) test (b). The diagram in c created using BioRender.com.

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