Fig. 7: Immunogenomics as a theranostic tool in the immunotherapy contexture.

a Heatmap of the 267 PPGL tumors profiled by RNA-Seq and classified into the four distinct TME subtypes described Bagaev et al. based on unsupervised k-means clustering of the 29 Fge enrichment scores. Genomic and clinical features are exhibited as depicted in the legend. b Kaplan–Meier plot of time to progression in patients according to the primary tumor TME subtype (n = 33 for IE, n = 55 for F, n = 74 for IE/F and n = 62 for D). Only primary tumors from non-metastatic and metastatic patients included. P-value was calculated using a log-rank test. Patients without evidence of metastases were censored at the date of the last follow-up. c Expression (median normalized z-score expression) of main immunoregulators (IMs) according to the clinical behavior and genomic subtype. Two-sided MWW and two-sided Krustal-Wallis tests were applied to test for differences between metastatic (n = 55) and non-metastatic (n = 176) primary tumors and between the different genomic subtypes (pseudohypoxic, n = 33; kinase signaling, n = 16; Wnt-altered, n = 6) within metastatic primary tumors, respectively; both tests were applied on the normalized data. Significant P-values are shown. d Representative images (top) and quantification (bottom) of PD-L1 IHC staining in a subset of n = 44 PPGLs. Quantification is represented for each genomic subtype. Two-sided Freeman–Halton test was used to test for differences between groups. Only MAML3 class exhibited statistically significant differences compared to the other groups. Scale bar in images = 150 μm. e Neoantigen load across genomic subtypes in primary tumors (n = 170). Only tumors with WES and RNA-Seq data available were included in the analysis; WT Wwnt-altered tumors have not been represented. The median value is marked and Tukey whiskers are represented. P-values shown in the figure correspond to two-sided MWW test. Only MAML3 class exhibited statistically significant differences compared to the other groups. f Percentages of CD8+ T cells infiltrated among the tumor cells detected by immunohistochemistry in a subset of n = 42 PPGLs with different genomic subtypes. For two cases, IHC was not assessable. Median ± IQR is shown. MWW was applied to test for differences between groups. See also Supplementary Figs. 11–13. Source data are provided as a Source Data file.