[Cited FineTest ELISA Kit] Current Research on Immunotherapy Cancer Treatment

FineTest ELISA kit contributes to the research on immunotherapy cancer treatment. The immunoassay is designed to measure MDA concentration in cell lysates.

Publication Details
Article Title: Inhibition of ACLY overcomes cancer immunotherapy resistance via polyunsaturated fatty acids peroxidation and cGAS-STING activation
Journal Title: Science Advances
DOI: 10.1126/sciadv.adi2465
IF: 13.6
PMID: 38055816

Abstract:     Adenosine 5'-triphosphate citrate lyase (ACLY) is a cytosolic enzyme that converts citrate into acetyl-coenzyme A for fatty acid and cholesterol biosynthesis. ACLY is up-regulated or activated in many cancers, and targeting ACLY by inhibitors holds promise as potential cancer therapy. However, the role of ACLY in cancer immunity regulation remains poorly understood. Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Mechanistically, ACLY inhibition causes polyunsaturated fatty acid (PUFA) peroxidation and mitochondrial damage, which triggers mitochondrial DNA leakage to activate the cGAS-STING innate immune pathway. Pharmacological and genetic inhibition of ACLY overcomes cancer resistance to anti-PD-L1 therapy in a cGAS-dependent manner. Furthermore, dietary PUFA supplementation mirrors the enhanced efficacy of PD-L1 blockade by ACLY inhibition. These findings reveal an immunomodulatory role of ACLY and provide combinatorial strategies to overcome immunotherapy resistance in tumors.

Keywords:  Immunotherapy Cancer Treatment, Drug Therapy, Immunosuppression

Immunoassay

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Figure Source: Sci Adv. 2023 Dec 8;9(49):eadi2465. doi: 10.1126/sciadv.adi2465.