Fig. 3

Intra-tumor heterogeneity of immune pathway. a, b Dysregulated immune pathways identified by over-representation analysis (a) and single-sample Gene Set Enrichment Analysis (ssGSEA) (b). For each patient, the tumor location is indicated (A: apex; B: side wall; C: costo-diaphragmatic; D: highest metabolic site). The immunologic status “hot” or “cold” was determined based on clusterization of stromal and immune cell infiltration (see Fig. 4). Over-representation of each pathway linked to immune communication is indicated as a circle, whose size is proportional to the gene ratio and the color gradient represents the FDR p-values (a). The differences in the ssGSEA score (delta_score) of each paired tumor sample are indicated as a color gradient (b). c The differential expression between paired tumor samples of immune checkpoints is shown in the heatmap. Differential expression was set to 0 for genes which did not display an FPKM score higher than 1 in at least one of the paired biopsies. The differentially expressed genes with a fold change of at least 2 are framed in blue. The genes encoding PDL1 (CD274), CTLA4 (CTLA4), and PD1 (PDCD1) are indicated by a blue arrow