A tumor-intrinsic WNT-inhibitory NOTUM program drives immune resistance in microsatellite stable colorectal cancer.

Furthermore, pathological tumor (pT) staging analysis showed that, while revCSC- and proCSC-specific transcription was abundant across all pT stages, the expression of WICC genes, such as NOTUM, NKD1, and APCDD1, was markedly enriched in pT4 tumors, followed by pT3, and was largely absent in pT2 and pT1 cases, although these differences did not reach statistical significance when assessed as proportions of WICCs at the individual patient level, likely due to limited cohort size ( Figures 2 C and S4 B).

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Nevertheless, inspection of survival trajectories showed a trend whereby tumors enriched for revCSC exhibited poorer outcomes, particularly within the WICC-low context, consistent with the fact that these patients were treated with conventional therapies.

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