Fig. 6: Immune landscape in PPGLs.

a Classification of immune subtypes within tumor tissue types and genomic subtype. The proportion (%) of samples of each immune subtype per tumor type and genomic subtype is shown. Aggressive tumors were excluded from pie charts due to the low number of samples available. b Plot showing the −log₁₀(P) resulting from a two-sided MWW analysis to define differences between metastatic primary versus non-metastatic tumors in the different immune cell classes estimated with CIBERSORTx. The ‘sign(effect)’ indicates the direction of the fold-change between the proportions in both groups. Cell types with >85% of the samples with ‘0 s’ were excluded from the analysis. Columns that surpass the red dashed line have P < 0.05. The top row summarizes univariate logistic regression analysis comparing immune cell proportions and metastatic risk. The color of the cell is relative to the −log₁₀(OR), and * indicates P < 0.05. c Percentage of CD8+ T cells infiltrated among tumor cells detected by immunohistochemistry (left) in a subset of n = 39 PPGLs with different clinical behavior. Three PPGLs classified as aggressive were not included in this analysis, and for two cases IHC were not assessable. Median ± IQR is shown. Two-sided MWW was applied to test for differences. Representative images (right) of CD8 IHC. Scale bar in images = 200 μm. d Top panel: median enrichment score of the different Fges in metastatic and non-metastatic primary tumors. Two-sided MWW was applied to test for differences between metastatic (n = 55) and non-metastatic (n = 176) primary tumors; significant P values are shown. Univariate (black) and multivariate (blue) logistic and Cox regression analysis of metastasis risk (middle panel) and TTP (bottom panel), respectively. Enrichment scores were used as a continuous variable. Multivariate analysis included genomic subtype as covariate. Only data from primary tumors from non-metastatic and metastatic patients were included. Significant associations in Fges scores after multivariate analysis are shaded in blue. e Kaplan–Meier plots of time to progression in patients according to different immune cell type levels found in primary tumors. Only primary tumors from non-metastatic and metastatic patients included. High levels (above the median level of the whole group) are represented in red (n = 92, n = 113, and n = 107, respectively for NK resting, NK activated and T regulatory) and low expression (below the median level) in blue (n = 130, n = 109 and n = 115, respectively for NK resting, NK activated and T regulatory). P-values shown inside the plots were calculated using a log-rank test. Patients without evidence of metastases were censored at the date of the last follow-up. See Supplementary Fig. 10 for the extended version. Source data are provided as a Source Data file.