Immune detection of cancer cells (via Cancer Discovery)

Upregulated transcription factor SOX17 aids early colorectal adenomas and cancers in immune escape. Goto et al. orthotopically transplanted mouse colonic organoids harboring Apc-null, KrasG12D, and Trp53-null mutations (naïve AKP organoids) into immunocompetent mice, passaged them 4-6 times and then retrieved primary tumor-derived AKP organoids. Compared to naïve AKP organoids, tumor-derived organoids showed significant upregulation of SOX17, which was also expressed in premalignant adenomas and early-stage colorectal tumors from human patients. Deletion of Sox17 through CRISPR-Cas9 editing in tumor-derived AKP organoids inhibited tumor growth in immunocompetent, but not immunodeficient, mice. The few Sox17-null tumors that did grow contained more interferon-γ (IFNγ)-producing effector-like T cells than wildtype counterparts. The authors further showed that SOX17 suppressed tumor cells’ ability to sense and respond to IFNγ and that SOX17 repressed the expression of LGR5 and major histocompatibility complex class I for immune evasion. The...

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