Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu HL
PROVIDER: S-EPMC9044757 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The success of immune-checkpoint blockade and chimeric antigen receptor (CAR) T cell therapies has established the remarkable capacity of the immune system to fight cancer. Over the past several years, it has become clear that immune cell responses to cancer are critically dependent upon metabolic programs that are specific to both immune cell type and function. Metabolic features of cancer cells and the tumor microenvironment impose constraints on immune cell metabolism that can favor immunosuppressive phenotypes and block antitumor responses. Advances in both preclinical and clinical studies have demonstrated that metabolic interventions can dramatically enhance the efficacy of immune-based therapies for cancer. As such, understanding the metabolic requirements of immune cells in the tumor microenvironment, as well as the limitations imposed therein, can have significant benefits for informing both current practice and future research in cancer immunotherapy.
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Project description:BackgroundOne-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune-related adverse events in patients.MethodsWe collected numerous literatures to explain the roles of one-carbon metabolism in cancer immunotherapy.ResultsIn this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future.ConclusionTargeting one-carbon metabolism is useful for cancer immunotherapy.
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Project description:(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01-0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg/gm clobetasol ointment. (4) Conclusions: The cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.
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