Fig. 1: Identification of tumor immune infiltration patterns in brain metastases.
a Schematic representation of patient sample collection and the experimental procedures performed. Immunohistochemistry (IHC), whole exome squencing (WES), cerebrospinal fluid (CSF). b Stacked bar plot showing the patient distribution of primary tumor of origin of the BrM (see cancer type acronyms in Supplementary Fig. 1e). c Heatmap representing the enrichment scores of seven immune cell types (rows) in 48 BrM patients (columns). IFNγ signature enrichment score has also been represented, in a distinct color scale (see color legend) (see the expression levels by gene in Supplementary Fig. 1g). On top, dendrogram of sample aggregation, according to the enrichment of the seven immune cell types, is shown. Three main clusters have been highlighted (low, intermediate, high); according to the degree of overall infiltration across cell types. On the left, dendrogram of immune cell type aggregation is shown. BrM primary tumor of origin is shown below, following the color scale in c. Sample IDs have been colored according to its clustering (blue: low, red: intermediate and high). Cytotoxic lymphocyte (CLym), tumor-associated macrophage (TAM), T cell regulatory (Treg), dendritic cell (DC), signature (sign). d Boxplot representing the IFNγ enrichment score distribution across the three clusters of tumor immune infiltration, as shown in d. Statistically significant differences are shown with an asterisk (P value < 0.05, T-test). All boxplots indicate median (center line), 25th and 75th percentiles (bounds of box), and minimum and maximum (whiskers). e Representative images of low, intermediate, and high CD8 staining by IHC (n = 42 patients). Scale bar, 55 µm. f Regression plots representing the Pearson correlation between CLym (left)/IFNγ signature (middle) enrichment score and CD8 IHC cell density (log2 transformed) (n = 42 patients). Each dot represents a unique patient sample, Pearson test results are shown (R2 and P value as an asterisk if <0.05), C.I., by performing a multilevel bootstrap, have also been displayed as shaded areas. Right panel represents the Pearson correlation between CLym and IFNγ signature enrichment, samples have been colored according to immune clustering, as shown in c, C.I. are also displayed.
