TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer

In MSS CRC, p53 deficiency is consistently associated with immunometabolic remodeling marked by persistent mTOR pathway activation, relative autophagy attenuation, and FOXP3-dominant immune-cold features across transcriptomic, single-cell, and proteomic layers. These findings add protein- and phosphosite-level evidence linking TP53 loss to an immune-suppressive metabolic state and support biomarker-guided evaluation of mTOR kinase (TORC1/2) inhibition, which more fully suppresses 4E-BP/S6K phosphorylation, combined with PD-1/PD-L1 (± CTLA-4) blockade in TP53-deficient MSS CRC.