Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40595642.
- Also identified by DOI 10.1038/s41467-025-60958-0 and PMC identifier 12216989.
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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<sup>+</sup> 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<sup>+</sup> 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.
Medical subject headings
- Kynurenine
- Colorectal Neoplasms
- Caffeine
- CD8-Positive T-Lymphocytes