ArticleProceedings of the National Academy of Sciences of the United States of America2022
D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 225 citations in OpenAlex.
- Bibliometric analysis of targeted immunotherapy for osteosarcoma-current knowledge, hotspots and future perspectives.Frontiers in immunology · 2024Pooled it
- Laser-Generated Ultrashort Pulsed Electron Beams Induce p53-Related Alteration of DNA Repair and Cell Death Pathways in Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2026Article
- PGK1-driven histone lactylation fuels MDSC-driven immune evasion and tumor progression in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Negative Emotions Induce Urticaria by Regulating Metabolites: A Two-Step Mendelian Randomization Study.Dermatology practical & conceptual · 2026Article
- Michelolide Enhances the Anticancer Efficacy of Radiation by Downregulating PD-L1 Protein Levels in Tumor Cells.International journal of molecular sciences · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Review
- Targeting CAFs-derived PCSK6 inhibits redistribution of PD-L1 and restores response of CD8Cell death and differentiation · 2026Article
- MS1-96 induces HIP1R-dependent PD-L1 degradation and promotes antitumor immunity in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS-STING pathway: mechanisms, challenges, and combination therapy strategies.Molecular cancer · 2026Review
- Proanthocyanidins enhance antitumor immunity by promoting ubiquitin-proteasomal PD-L1 degradation via stabilization of LKB1 and SYVN1.The Journal of clinical investigation · 2026Article
- Targeting glucocorticoid receptor to enhance immunotherapy response in triple negative breast cancer.Breast cancer research : BCR · 2026Article
- Paroxetine repurposing enhances antitumor immunity via SPOP-mediated PD-L1 ubiquitination and proteasomal degradation.Journal of experimental & clinical cancer research : CR · 2026Article
- The central role of radiotherapy in remodeling the tumor immune microenvironment: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Developing immunotherapies through glycosylation reprogramming to combat solid cancers.Frontiers in immunology · 2026Review
- The role of the tumor microenvironment in mediating radiopharmaceutical therapy: bridging nuclear medicine and cancer immunotherapy.Military Medical Research · 2026Review
- Glucose metabolic reprogramming: a novel strategy to enhance radiotherapy response to triple-negative breast cancer.Frontiers in public health · 2026Review
- Regulation of glycosylation in radiotherapy: exploring the multiple effects of DNA damage, immune response, stromal microenvironment and metabolism.Frontiers in oncology · 2026Review
- Butyrate enhances tumor immune evasion by increasing PD-L1 abundance.International journal of biological sciences · 2026Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is the most frequent malignancy in women worldwide, and triple-negative breast cancer (TNBC) patients have the worst prognosis and highest risk of recurrence. The therapeutic strategies for TNBC are limited. It is urgent to develop new methods to enhance the efficacy of TNBC treatment. Previous studies demonstrated that D-mannose, a hexose, can enhance chemotherapy in cancer and suppress the immunopathology of autoimmune diseases. Here, we show that D-mannose can significantly facilitate TNBC treatment via degradation of PD-L1. Specifically, D-mannose can activate AMP-activated protein kinase (AMPK) to phosphorylate PD-L1 at S195, which leads to abnormal glycosylation and proteasomal degradation of PD-L1. D-mannose-mediated PD-L1 degradation promotes T cell activation and T cell killing of tumor cells. The combination of D-mannose and PD-1 blockade therapy dramatically inhibits TNBC growth and extends the lifespan of tumor-bearing mice. Moreover, D-mannose-induced PD-L1 degradation also results in messenger RNA destabilization of DNA damage repair-related genes, thereby sensitizing breast cancer cells to ionizing radiation (IR) treatment and facilitating radiotherapy of TNBC in mice. Of note, the effective level of D-mannose can be easily achieved by oral administration in mice. Our study unveils a mechanism by which D-mannose targets PD-L1 for degradation and provides methods to facilitate immunotherapy and radiotherapy in TNBC. This function of D-mannose may be useful for clinical treatment of TNBC.
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