Figure 7.

A Ly6E^(hi) neutrophil-derived gene signature outperforms pre-existing biomarkers in the prediction of immunotherapy response

(A) Bulk RNA-seq expression profiles were obtained from 1,440 publicly available samples from 11 datasets across 6 cancer types^37,38,39,40 (see STAR Methods) and scored for a 15-gene Ly6E^(hi)-signature (Neut_IFN-15) (top) or a previously published 6-gene IFNγ-signature⁴¹ (bottom). A heatmap of median, normalized enrichment scores for each dataset is shown and significant differences between groups were tested (NR vs. R). Samples were taken either pre-treatment (PRE) or post-treatment (POST). Raw data are available in Figure S10. BLCA = urothelial bladder cancer; GBM = glioblastoma multiforme; NSCLC = non-small cell lung cancer; RCC = renal cell carcinoma; SKCM = skin cutaneous melanoma; STAD = stomach adenocarcinoma. Significance was assessed by means of a one-way Mann-Whitney test (NS, p > 0.01; ^∗, p < 0.01; ^∗∗, p < 0.001, ^∗∗∗, p < 0.0001).

(B) Smoothed area under the curve (AUC)-receiver operating characteristics (ROC) plots for total tumor mutation burden (tTMB) (95% CIs: 0.4865-0.6722), Age (95% CIs: 0.4374-0.5766), PDL1 immunohistochemistry (IHC) (95% CIs: 0.5534-0.7172), STK11 mutational status (95% CIs: 0.5246-0.6874), KEAP1 mutational status (95% CIs: 0.5334-0.7085), IFNγ-6 signature scores (95% CIs: 0.6253-0.7561) and Ly6E^(hi) Neut_IFN-15 signature scores (95% CIs: 0.7714-0.9105) in data from the OAK NSCLC study³⁹ (NR vs. R). Confidence intervals were determined using 1,000 stratified, bootstrap replicates.