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Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer

Author

Listed:
  • Yuechen Liu

    (Southern Medical University
    Southern Medical University)

  • Zhengyu Liu

    (Southern Medical University
    Southern Medical University)

  • Yating Hu

    (Southern Medical University
    Southern Medical University)

  • Yunyan Ling

    (Southern Medical University)

  • Shunjie Qing

    (Southern Medical University
    Southern Medical University)

  • Yang Liu

    (Southern Medical University)

  • Yizhi Zhan

    (Southern Medical University)

  • Zhiyong Shen

    (Southern Medical University
    Southern Medical University)

  • Yuan Fang

    (Southern Medical University)

  • Haijun Deng

    (Southern Medical University
    Southern Medical University)

Abstract

Colorectal cancer (CRC) is a leading global health issue, ranking third in incidence and second in cancer mortality. Immunotherapy, effective mainly in mismatch repair-deficient CRC, may benefit from dietary interventions. This study investigates caffeine’s potential to boost programmed death-1 (PD-1) immunotherapy efficacy in CRC, revealing that caffeine significantly reduces tumor growth, extends survival, and enhances CD8+ T cell activity in CRC by suppressing kynurenine pathway. Mechanistically, caffeine decreases kynurenine via the Krüppel-like factor 4 (KLF4)- Collagen type XII alpha 1 (COL12A1)- Mitogen-Activated Protein Kinase (MAPK)-Indoleamine 2,3-dioxygenase 1 (IDO1) axis, mitigating CD8+ T cell exhaustion. Combining caffeine with PD-1 therapy further prolongs survival, highlighting the value of integrating nutritional strategies into cancer treatment to improve outcomes and broaden therapeutic options. Here, we show caffeine can enhance PD-1 immunotherapy in CRC by suppressing kynurenine pathway, suggesting its potential as an adjunctive dietary therapy.

Suggested Citation

  • Yuechen Liu & Zhengyu Liu & Yating Hu & Yunyan Ling & Shunjie Qing & Yang Liu & Yizhi Zhan & Zhiyong Shen & Yuan Fang & Haijun Deng, 2025. "Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60958-0
    DOI: 10.1038/s41467-025-60958-0
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