Method Profile
Test whether removing a WICC tumor-cell population or adding back NOTUM changes antigen-specific T-cell killing.
Investigate tumor-mediated immune resistance and candidate ways to restore cytotoxic activity.
Murine AKP colorectal tumoroids with a defined ovalbumin antigen and OT-I CD8-positive T cells; separate human tumor/organoid analyses identify the WICC state.
WICC depletion with or without T cells, recombinant NOTUM rescue and viability/spatial imaging.
Tumor system
Mouse tumoroids with Apc/Trp53 loss and mutant Kras.
Effector system
Antigen-specific OT-I CD8-positive T cells.
Perturbations
Selective WICC depletion and recombinant NOTUM add-back; separate Notum-deficient comparisons.
Compare depletion alone, T cells alone and their combination, then use NOTUM add-back to test the secreted-factor contribution.
Functional depletion and rescue experiments in a defined mouse coculture.
Viability distributions were evaluated in four independent experiments; spatial/rescue comparisons used three.
WICC-intact/depleted tumoroids with or without T cells and NOTUM add-back.
WICC depletion with T cells increased killing; recombinant NOTUM increased tumoroid survival.
Human tumor analyses identified a WNT-inhibitory cancer-cell state. Mouse tumoroid–T-cell experiments then tested how removing that population or its secreted factor changed immune killing.
