figshare
Browse
cir-22-1023_supplementary_table_5_suppst5.pdf (60.5 kB)

Supplementary Table 5 from RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma

Download (60.5 kB)
journal contribution
posted on 2024-02-02, 08:20 authored by Pengfei Yu, Shuwen Cao, Shyh-Ming Yang, Ganesha Rai, Natalia J. Martinez, Adam Yasgar, Alexey V. 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

Tissue pharmacokinetics and bio-distribution of C86 at two different does through the intraperitoneal route.

Funding

U.S. Department of Defense (DOD)

National Institutes of Health (NIH)

Cancer Research Institute (CRI)

Burrows Welcome Fund

History

ARTICLE 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.

Usage metrics

    Cancer Immunology Research

    Categories

    Keywords

    Gastrointestinal CancersLiver cancerImmunotherapyTumor Microenvironment

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC