Using a large cohort of colorectal cancer organoids (CCOs) that faithfully preserve primary tumor genetics, including TP53, KRAS, APC and crucially FBXW7 mutations, Cho and colleagues defined a cancer-intrinsic immuno-genomic profile marked by high HLA-II mRNA expression, which strongly predicts superior overall and recurrence-free survival. The gene discussed is APC; the disease is neoplasm.