A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression

Plebanek, Michael P.; Xue, Yue; Nguyen, Y‐Van; DeVito, Nicholas C.; Wang, X F; Holtzhausen, Alisha; Beasley, Georgia M.; Theivanthiran, Balamayooran; Hanks, Brent A.

doi:10.1126/sciimmunol.adi4191

articleScience ImmunologyMay 10, 2024GREEN OA

A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression

MPMichael P. Plebanek YXYue Xue YNY‐Van Nguyen NCNicholas C. DeVito XFX F Wang

Duke Medical Center · Duke University · +1 more institution

PubMed

Indexed incrossrefpubmed

Abstract

Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specific surface marker, we demonstrate that mature regulatory DCs (mregDCs) migrate to tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 and regulatory T cell differentiation. Transcriptional and metabolic studies showed that mregDC functionality is dependent on the mevalonate biosynthetic pathway and its master transcription factor, SREBP2. We found that melanoma-derived lactate activates SREBP2 in…

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106

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References: 75

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Topics & keywords

Topics

Keywords

Tumor microenvironment
Biology
Cancer research
Melanoma
Dendritic cell
FOXP3
Immune system
Cross-presentation

UN Sustainable Development Goals

Good health and well-being

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