ArticleCancer discovery2023
Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 43 citations in OpenAlex.
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- ZBTB21 Is a Dual Suppressor of Pyroptosis and MHC-I Antigen Presentation That Promotes Tumor Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolism modulates stress and neoplasia.Nature metabolism · 2026Article
- ALDH1L2 regulates reactive oxygen species and acinar-to-ductal metaplasia in the pancreas.Nature metabolism · 2026Article
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Semaphorins: from CD8⁺ T cells to cancer immunotherapy.Biomarker research · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Proliferative double-negative T (DNT)-cell responses to PD-1 blockade therapy were positively correlated with good clinical outcomes in non-small cell lung cancer patients.Pakistan journal of medical sciences · 2026Article
- Drug Delivery Engineering Strategies Targeting CD4+/CD8+ T Cell Exhaustion to Improve the Tumor Immunosuppressive Microenvironment.International journal of nanomedicine · 2026Review
- Folate metabolism-based risk stratification identifies CYP27B1 as a determinant of tumor progression in HNSCC.Frontiers in medicine · 2026Article
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy.Theranostics · 2026Review
- Gut microbial metabolites in cancer immunomodulation.Molecular cancer · 2025Review
- CIMT 2025: Report on the 22Human vaccines & immunotherapeutics · 2025Article
- Therapeutic targeting of cell death-immune crosstalk in cancer to rewire the tumor immune microenvironment.Molecular cancer · 2025Review
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- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide.Nature metabolism · 2025Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The tumor microenvironment (TME) restricts antitumor CD8+ T-cell function and immunotherapy responses. Cancer cells compromise the metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate that one-carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T-cell fitness and antitumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T-cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for enhanced tumor control. Our data demonstrate that formate provides metabolic support to CD8+ T cells reinvigorated by anti-PD-1 to overcome a metabolic vulnerability in 1C metabolism in the TME to further improve T-cell function. SIGNIFICANCE: This study identifies that deficiencies in 1C metabolism limit the efficacy of PD-1 blockade in B16-OVA tumors. Supplementing 1C metabolism with formate during anti-PD-1 therapy enhances CD8+ T-cell fitness in the TME and CD8+ T-cell-mediated tumor clearance. These findings demonstrate that formate supplementation can enhance exhausted CD8+ T-cell function. See related commentary by Lin et al., p. 2507. This article is featured in Selected Articles from This Issue, p. 2489.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.