Dietary restriction reprograms CD8+ T cell fate to enhance anti-tumour immunity and immunotherapy responses
Bibliographic record
Abstract
Abstract Reducing calorie intake through dietary restriction (DR) slows tumour growth in mammals, yet the underlying mechanisms are poorly defined. Here, we show that DR enhances anti-tumour immunity by optimizing CD8 + T cell function within the tumour microenvironment (TME). Using syngeneic xenograft tumour models, we found that DR induces a profound reprogramming of CD8 + T cell fate in the TME, favouring the expansion of effector T cell subsets with enhanced metabolic capacity and cytotoxic potential, while limiting the accumulation of terminally exhausted T cells. This metabolic reprogramming is driven by enhanced ketone body oxidation, particularly β-hydroxybutyrate (βOHB), which is elevated in both the circulation and tumour tissues of DR-fed mice. βOHB fuels T cell oxidative metabolism under DR, increasing mitochondrial membrane potential and tricarboxylic acid cycle-dependent pathways critical for T cell effector function, including acetyl-CoA production. By contrast, T cells deficient for ketone body oxidation exhibit reduced mitochondrial function, increased exhaustion and fail to control tumour growth under DR conditions. Importantly, DR synergizes with anti-PD1 immunotherapy, further augmenting anti-tumour T cell responses and limiting tumour progression. Our findings reveal that T cell metabolic reprogramming is central to the anti-tumour effects of DR, highlighting nutritional control of CD8 + T cell fate as a key driver of anti-tumour immunity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".