The abstract is read at the publisher; the summary is JClub's.
Ketogenic fasting (KF) sensitizes immune-refractory tumor models to PD-1 blockade by preserving intratumoral glutamine while remodeling microbiota metabolites, enabling stronger cytotoxic lymphocyte activity.
- Why it matters: Many tumors resist immune checkpoint blockade, and tumor metabolic conditions can suppress cytotoxic lymphocytes; this work targets diet-driven immunometabolic and microbial mechanisms that may restore responsiveness.
- What they did: The authors combined ketogenic diet and intermittent fasting (KF) and used single-cell transcriptomics to define KF-associated cytotoxic lymphocyte states, while testing microbiota depletion, fecal transfer, and monocolonization with Odoribacter splanchnicus.
- The result: KF increased SLC38A1/SLC38A2-linked glutamine access and interferon-STAT1 signaling in tumor-infiltrating CD8+ T cells and NK cells, and O. splanchnicus restored tumor control in microbiota-depleted hosts via polyamine remodeling and indole-3-lactic acid.
The findingWhy it mattersWhat they didThe result
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