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

ABSTRACT 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 CD 8+ 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 CD 8+ 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.