Fig. 5

Characterization of immune infiltration clusters in ccRCC. a Unsupervised clustering of 415 ccRCC patients from the TCGA cohort using ssGSEA scores from 24 immune cell types, three immunotherapy targets (PD-1, PD-L1, CTLA-4), and angiogenesis. Hierarchical clustering was performed with Euclidean distance and Ward linkage. We discover three distinct immune infiltration clusters, here termed (1) non-infiltrated, (2) heterogeneously infiltrated, and (3) T cell enriched. The T cell enriched cluster is characterized by tumors with high APM scores and high granzyme B and interferon gamma mRNA expression levels. b Differential expression analysis with Mann–Whitney test for all genes in the TCGA RNA-Seq dataset excluding signature genes. Only genes that are significantly overexpressed in one cluster at a q-value cutoff of 5 × 10^–5 are shown. Pathway analysis using DAVID [44] reveals that the genes overexpressed in the three clusters (n = 1110, 181, and 277, respectively) are enriched in (1) adaptive and innate immune response, (2) angiogenesis, and (3) mitochondrial and metabolic processes. c Differential expression analysis with Mann–Whitney test for all proteins in the TCGA reverse phase protein array (RPPA) dataset. Only proteins that are significantly overexpressed in one cluster at a q-value cutoff of 0.01 are shown. This analysis recapitulates the significant differences in immune response in the T cell enriched cluster and in angiogenesis in the heterogeneously infiltrated cluster. d PCA of the immune infiltration scores in ccRCC. The three clusters most likely reflect distinct biology