文章基本信息

标题：A mechanism of cooling hot tumors: Lactate attenuates inflammation in dendritic cells
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作者：Hisashi Kanemaru ; Yukari Mizukami ; Akira Kaneko 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-23
DOI：10.1016/j.isci.2021.103067
语种：English
出版社：Elsevier
摘要：SummaryTurning non-inflamed (cold) tumors into inflamed (hot) tumors is important for maximizing the effect of immune checkpoint inhibitors (ICIs) against malignancies. We showed that lactate, a product of the Warburg effect, inhibited the efficacy of ICIs and suppressed IL-12 p40 expression in dendritic cells (DCs) through reducing NF-κB p65, p50, and c-Rel DNA-binding activity to the IL-12 p40 promoter. Additionally, lactate promoted the expression of early growth response protein 1 (EGR1), whose expression was increased in human invasive melanoma compared with non-invasive melanoma. We also found that EGR1 interacts with serum response factor (SRF) and represses the expression of CD80 in DCs. These findings suggest that lactate and its induced EGR1 are key factors that turn hot tumors into cold tumors and may represent targets in cancer treatment with ICIs.Graphical abstractDisplay OmittedHighlights•Lactate suppressed IL-12 p40 expression in dendritic cells•Lactate promoted the expression of early growth response protein 1 (EGR1)•EGR1 interacts with serum response factor (SRF) and represses the expression of CD80•Lactate and EGR1 switch inflamed (hot) tumors to non-inflamed (cold) tumorsImmunology; Immune response; Cancer