{
  "abstract": "Background Intermittent fasting (IF) has shown antitumor activity in preclinical models, but the mechanisms linking nutrient restriction to tumor vulnerability and immune activation in colorectal cancer (CRC) remain unclear. To investigate whether IF suppresses CRC progression by altering taurine availability and PERK-dependent endoplasmic reticulum (ER) stress adaptation, and to determine how these changes affect antitumor immunity and response to anti–PD-1 therapy.Methods CRC was studied in AOM–DSS mice and syngeneic MC38 and CT26 tumor models under ad libitum feeding or a 5:2 IF regimen. Tumor growth, histopathology, and proliferation were assessed by gross examination, H&E staining, and Ki-67 analysis. Bulk RNA sequencing, metabolomics, immunofluorescence, flow cytometry, and ELISA were used to evaluate metabolic and immune changes. Taurine supplementation, CD8 depletion, and PERK or ERO1A genetic manipulation were performed for mechanistic validation.Results IF significantly reduced tumor burden and proliferation in both inflammation-driven and syngeneic CRC models ( IDDF2026-ABS-0126 Figure 1. Intermittent fasting suppresses colorectal tumorigenesis in mouse models). IF increased intratumoral CD8+ T-cell infiltration and cytotoxic activity, accompanied by elevated circulating HMGB1, calreticulin, and annexin A1. Metabolomic profiling identified taurine as a markedly reduced metabolite in both serum and tumor tissues under IF, together with decreased expression of the taurine transporter SLC6A6. Taurine supplementation partially reversed the tumor-suppressive effect of IF. Mechanistically, taurine interacted with GRP78, and taurine depletion was associated with reduced PERK stability and decreased ERO1A expression under nutrient stress. Genetic suppression of PERK or ERO1A phenocopied IF, promoting vacuolization, immunogenic stress-associated signals, enhanced CD8+ T-cell infiltration, and tumor suppression. IF also improved the efficacy of anti–PD-1 therapy.Conclusions IF suppresses CRC growth and enhances antitumor immunity, at least in part, by reducing taurine availability and impairing PERK–ERO1A-mediated ER stress adaptation. These findings support dietary intervention as a potential strategy to increase tumor vulnerability and improve immunotherapy response in CRC.Abstract IDDF2026-ABS-0126 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Zhongshan Hospital, Fudan University, China"
      ],
      "name": "Baohui Song"
    },
    {
      "affiliations": [
        "Zhongshan Hospital, Fudan University, China"
      ],
      "name": "Sikei Kam"
    },
    {
      "affiliations": [
        "Zhongshan Hospital, Fudan University, China"
      ],
      "name": "Pinghong Zhou"
    },
    {
      "affiliations": [
        "Zhongshan Hospital, Fudan University, China"
      ],
      "name": "Yunshi Zhong"
    },
    {
      "affiliations": [
        "Zhongshan Hospital, Fudan University, China"
      ],
      "name": "Mingyan Cai"
    }
  ],
  "title": "IDDF2026-ABS-0126 Intermittent fasting induces perk-mediated paraptosis and antitumor immunity in colorectal cancer",
  "uid": "586a9dae-45d0-5e32-85e4-3efef028711e"
}