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However, it remains unclear the role of calcium channel inhibitors in tumor immunomodulation. Here, calcium channel blocker lacidipine is identified to potently inhibit the enzymatic activity and expression of indoleamine 2,3\u2010dioxygenase 1 (IDO1), a rate\u2010limiting enzyme in tryptophan metabolism. Lacidipine activates effector T cells and incapacitates regulatory T cells (Tregs) to augment the anti\u2010tumor effect of chemotherapeutic agents in breast cancer by converting immunologically \u201ccold\u201d into \u201chot\u201d tumors. Mechanistically, lacidipine targets calcium channels (Ca<jats:sub>V<\/jats:sub>1.2\/1.3) to inhibit Pyk2\u2010JAK1\u2010calmodulin complex\u2010mediated IDO1 transcription suppression, which suppresses the kynurenine pathway and maintains the total nicotinamide adenine dinucleotide (NAD) pool by regulating NAD biosynthesis. These results reveal a new function of calcium channels in IDO1\u2010mediated tryptophan metabolism in tumor immunity and warrant further development of lacidipine for the metabolic immunotherapy in breast cancer.<\/jats:p>","DOI":"10.1002\/advs.202409310","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T12:39:30Z","timestamp":1732538370000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Calcium Channel Blocker Lacidipine Promotes Antitumor Immunity by Reprogramming Tryptophan Metabolism"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuwen","family":"Sheng","sequence":"first","affiliation":[{"name":"Center for Natural Products Research Chengdu Institute of Biology Chinese Academy of Sciences  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Qiao","sequence":"additional","affiliation":[{"name":"Center for Natural 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