Figure 4. The RSI describes distinct tumor immune microenvironments.

(a) RSI^lo versus RSI^hi tumors were compared with single sample gene set enrichment analysis (ssGSEA) using the MSigDB hallmark pathway genes related to immune signaling. Heatmap intensity depicts the -log p-value of the Fisher exact test multiplied by the directionality of expression difference; enriched in RSI^lo (red) or RSI^hi (blue). Tumor types are ordered by the immune score. (b) Tumor types are ordered by immune score and normalized CIBERSORT immune cell infiltrate estimates are compared within a given tumor type by dichotomizing at the median RSI value to identify RSI^lo and RSI^hi tumors. Immune cell infiltrates involved in the innate (left panel) and the adaptive (right panel) response. Hypothesis tests (Fisher’s exact test) in tumor types between RSI^hi and RSI^lo were performed; a black bar beneath the comparison denotes false-discovery rate adjusted q < 0.05. Black bars to the right of heatmap indicate proportion of significant tumor types for given immune cell infiltrate enrichment comparison between RSI^lo and RSI^hi tumors. (d) Associations of IFNα and the RSI with immune cell (IC) subtypes as independent or coordinated biology. Half-circles represent whether comparison within a tumor type and IC subtype are significant (q < 0.05); red (RSI vs IC), blue (IFNα vs IC). Empty circles imply no association between variables. Tumor types are ordered by immune score.