The solution to the paradox of colon cancers-which has the propensity to elicit and attract CD3+/CD8+ T cells (so called “high immunoscore”) but remains resistant to immunotherapy when devoid of mutated neoantigen-relies on two pillars, i) ileal apoptosis through activation of the executioner caspases, and ii) a proper ileal microbiome composition balancing immunogenic and tolerogenic commensals. Here, CD8A is linked to colonic neoplasm.