期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.989000
关键词
pharmacological ascorbate; immune regulation; anti-PD-1; cancer immunotherapy; immune checkpoint inhibitors; antioxidant therapy; prooxidant therapy
类别
资金
- NCI [P01CA217797, P30CA086862]
- Gateway for Cancer Research [G-17-1500T32 GM007337]
- UIHCCCOM Iowa Aging Initiative
- NIAID [R21AI157121]
- NIH/NCI [T32CA078586]
- Holden Comprehensive Cancer Center Gift Funds
Pharmacological ascorbate, with its dual redox roles and immune modulating functions, shows potential as an adjuvant to standard anti-cancer treatments and could enhance the efficacy of immune checkpoint inhibitors.
Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching similar to 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues. Immune checkpoint inhibitors (ICIs) are highly promising therapies for many cancer patients but face several challenges including low response rates, primary or acquired resistance, and toxicity. Ascorbate modulates both innate and adaptive immune functions and plays a key role in maintaining the balance between pro and anti-inflammatory states. Furthermore, the success of pharmacological ascorbate as a radiosensitizer and a chemosensitizer in pre-clinical studies and early phase clinical trials suggests that it may also enhance the efficacy and expand the benefits of ICIs.
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