In this week's Journal for ImmunoTherapy for Cancer, Arai and colleagues analyzed next-generation sequencing data for DNA and RNA from 14,287 patients with colorectal cancer (CRC) categorized by median CD47 expression level, and showed that CD47, a key component of innate immunity in deflecting phagocytosis, is associated with molecular subtypes of CRC, cell damage-associated molecular pattern-related genes, major oncogenic pathways, and adaptive immune checkpoint genes. Taken together, they concluded that CD47 expression is associated with activation of oncogenic pathways and an immune-engaged tumor microenvironment. Clinical outcomes data also demonstrated that high CD47 is associated with prolonged survival in patients treated with antiangiogenic and checkpoint inhibitor therapy. Biomarker studies such as this will enable broader application of immuno-oncology to patients with CRC and other malignancies.