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Enhanced Chemo-Immunotherapy Against Melanoma by Inhibition of Cholesterol Esterification in CD8

Enhanced Chemo-Immunotherapy Against Melanoma by Inhibition of Cholesterol Esterification in CD8

Man Li, Yuting Yang, Jiaojie Wei, Xingli Cun, Zhengze Lu, Yue Qiu, Zhirong Zhang, Qin He

Nanomedicine. 2018 Nov;14(8):2541-2550.

PMID: 30193815

Abstract:

Cholesterol facilitated the formation of T cell receptor on cytotoxic CD8+ T lymphocytes (CTLs). However, the activation of CD8+ T cells always resulted in the upregulation of acetyl-CoA acetyltransferase-1 (ACAT-1) and enhanced the esterification of cholesterol. To relieve the suppression on CD8+ T cells, an ACAT-1 inhibitor avasimibe was combined with chemo-immunotherapy. Paclitaxel and immunoadjuvant αGC were co-encapsulated in liposomes modified with pH sensitive TH peptide (PTX/αGC-TH-Lip). After intravenous injections, the combination of avasimibe significantly elevated the free cholesterol level and relieved the inhibition of CD8+ T cells caused by PTX/αGC-TH-Lip, leading to enhanced CTL responses and anti-tumor effects of PTX/αGC-TH-Lip in B16F10 melanoma xenograft and lung metastasis models. The adoptive immunotherapy further confirmed the enhanced anti-tumor immune responses of the combined strategy. The combination of avasimibe and PTX/αGC-TH-Lip was proven as a feasible approach to enhance the antitumor effects of chemo-immunotherapy by relieving the inhibition of CD8+ T cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP166518601	Avasimibe		166518-60-1	Price

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