肝细胞癌
癌症研究
免疫疗法
医学
免疫系统
癌症
肝癌
药理学
免疫学
内科学
作者
Pengfei Yu,Shuwen Cao,Shyh‐Ming Yang,Ganesha Rai,Natalia J. Martinez,Adam Yasgar,Alexey Zakharov,Anton Simeonov,William A. Molina Arocho,Graham P. Lobel,Hesham Mohei,Alexis L. Scott,Li Zhai,Emma E. Furth,M. Celeste Simon,Malay Haldar
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2023-12-04
卷期号:12 (2): 180-194
被引量:1
标识
DOI:10.1158/2326-6066.cir-22-1023
摘要
Abstract Globally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into protumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze RA biosynthesis. In this study, we have identified RALDH1 as the key driver of RA production in HCC and demonstrated the efficacy of RALDH1-selective inhibitors (Raldh1-INH) in suppressing RA production by HCC cells. Raldh1-INH restrained tumor growth in multiple mouse models of HCC by reducing the number and tumor-supporting functions of intratumoral macrophages as well as increasing T-cell infiltration and activation within tumors. Raldh1-INH also displayed favorable pharmacokinetic, pharmacodynamic, and toxicity profiles in mice thereby establishing them as promising new drug candidates for HCC immunotherapy.
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