Intermittent Fasting Reduces Taurine Availability and Promotes Antitumor Immunity Through PERK Attenuation-Associated Paraptosis-Like Cell Death in Colorectal Cancer.

Intermittent fasting (IF) exerts antitumor activity in colorectal cancer (CRC), but the tumor-intrinsic metabolic mechanism linking nutrient restriction to antitumor immunity remains unclear. In this study, IF reduced taurine availability and suppressed tumor growth in a CD8+ T cell-dependent manner. Taurine supplementation attenuated this effect, whereas pharmacological inhibition of taurine uptake partially recapitulated fasting-associated tumor suppression in preclinical models. Mechanistically, taurine is associated with the endoplasmic reticulum chaperone GRP78 and contributes to the maintenance of PERK abundance under nutrient stress. As a metabolic consequence of IF, taurine restriction impaired PERK stability, suppressed downstream ERO1A signaling, and redirected CRC cells from stress tolerance toward paraptosis-like immunogenic stress. PERK loss enhanced CD8+ T-cell activation, remodeled the tumor microenvironment toward a less suppressive state, and supported tumor control in combination with anti-PD-1 therapy. The present study identified taurine restriction as a functional metabolic feature of IF that compromises PERK-dependent stress adaptation and promotes antitumor immunity in CRC.