Extended Data Fig. 5: AC484 inflames the TME and enhances the repertoire of the tumor-directed T cell response.

a, Top positively or negatively enriched Hallmark gene signatures determined by GSEAPreranked on differentially expressed genes calculated by a logistic regression by condition. Dotted lines indicate FDR < 0.25. b, UMAP projections downsampled by condition of the Hallmark IFNγ Response gene set and T cell Inflamed Signature (left) (Methods). Violin plots showing quantification by condition, statistical significance <0.05 in an independent t test (right). c, Heatmap showing averaged pseudobulk expression of key pro-inflammatory and anti-inflammatory cytokines and chemokines and antigen processing-related genes by model. d, Number of 7–11 amino acid length peptides presented on MHC I of B16 tumour cells treated in vitro overnight with DMSO as control, 0.3 μM AC484 alone, 0.5 ng/mL IFNγ alone, and 0.5 ng/mL IFNγ + 0.3 μM AC484. e, Counts of unique CDR3 sequences captured in targeted PCR of α and β TCR transcript from bulk RNA of B16 untreated (n = 14), anti-PD-1 (n = 15), and AC484 (n = 15) treated tumours. f, Quantification of the number of clusters or recognition groups found in each replicate (left) and number of unique CDR3s per each cluster by replicate (right). g, CDR3 sequences amplified from B16 untreated, AC484, or anti-PD-1-treated tumours clustered by GLIPH2 into proposed antigen recognition groups, number of clusters (left) and unique CDR3 sequences per cluster (right).

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