ArticleProceedings of the National Academy of Sciences of the United States of America2020
High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Clinical benefits and risks of high-dose intravenous vitamin C: a systematic review.Journal of medicine and life · 2026Pooled it
- High-Dose Intravenous Vitamin C Combined with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase II Trial.Cancer research communications · 2024Trial
- Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.Redox biology · 2022Trial
- Effects of Molecular Iodine/Chemotherapy in the Immune Component of Breast Cancer Tumoral Microenvironment.Biomolecules · 2021Trial
- Endolysosomal routing combined with immune stimulation enhances anti-tumor efficacy of an HPV16 mRNA therapeutic vaccine.Materials today. Bio · 2026Article
- Ascorbate-driven quinone redox cycling as a pro-oxidant anticancer strategy.Redox biology · 2026Review
- Beyond redox: vitamin C in signaling, epigenetic regulation and protein modification-relevance to cancer therapy.Clinical epigenetics · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Vitamin C Conditioning Generates Tumor-Targeting CAR T Cells with Superior Cytotoxicity and Fitness in a Posttransplant Lymphoproliferative Disorder Tumor Model.Molecular cancer therapeutics · 2026Article
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- USP5 inhibition stimulates immunogenic ferroptosis that enhances immunotherapy in diffuse large B-cell lymphoma.Cell communication and signaling : CCS · 2026Article
- Physiological activation of Aryl hydrocarbon receptor by food-derived ligands is essential for the efficacy of anti-PD1 therapy.Nature communications · 2025Article
- Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.Antioxidants (Basel, Switzerland) · 2025Review
- Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma.Journal of translational medicine · 2025Article
- High-dose ascorbic acid selectively induces pyroptosis in LKB1-deficient lung cancer and sensitizes immunotherapy.Cell reports. Medicine · 2025Article
- Tuning the Chain Conformation of Pyrenyl-Pyridine Conjugated Oligomer Nanoprobe for Ultrasensitive Fluorescent Assaying of FeJournal of fluorescence · 2025Article
- Single-Cell Analysis Reveals that Vitamin C Inhibits Bone Metastasis of Renal Cancer via Cell Cycle Arrest and Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Synergistic and toxicity‑reducing effects of acteoside as an adjuvant therapy of oxaliplatin against hepatocellular carcinoma.International journal of oncology · 2025Article
- Effects of functional antioxidants on the expansion of gamma delta T-cells and their cellular cytotoxicity against bladder cancer cells.BMC cancer · 2025Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma coculture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intratumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intratumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intratumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and natural killer cells), and interleukin 12 production by antigen-presenting cells compared with single-agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.
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What OpenQuestion holds
Registered trials
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.