Tumor-intrinsic WNT/CTNNB1 activation typifies an ‘immune-excluded’ (non-inflamed) phenotype versus ‘inflamed’ tumors; tissue/genomic surrogates (e.g., CTNNB1 mutations, glutamine-synthetase staining or RNA signatures) should be encoded as negative-predictive contexts—modifying probabilities rather than imposing absolute rules—when estimating ICI benefit (Nguyen Hoang et al., 2025; Chen Y. et al., 2024; Fu et al., 2023). Here, CTNNB1 is linked to neoplasm.