國家衛生研究院 NHRI:Item 3990099045/15078
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 906852      Online Users : 911
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15078


    Title: A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment
    Authors: Ye, PH;Li, CY;Cheng, HY;Anuraga, G;Wang, CY;Chen, FW;Yang, SJ;Lee, KT;Chang, KY;Lai, MD
    Contributors: National Institute of Cancer Research
    Abstract: Tumor progression is dependent on tumor cells and their microenvironment. It is important to identify therapies that inhibit cancer cells and activate immune cells. Arginine modulation plays a dual role in cancer ther-apy. Arginase inhibition induced an anti-tumor effect via T-cell activation through an increase in arginine in the tumor environment. In contrast, arginine depletion by arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG 20) induced an anti-tumor response in argininosuccinate synthase 1 (ASS1)-deficient tumor cells. ADI-PEG 20 did not cause toxicity to normal immune cells, which can recycle the ADI-degraded prod-uct citrulline back to arginine. To target tumor cells and their neighboring immune cells, we hypothesized that the combination of an arginase inhibitor (L-Norvaline) and ADI-PEG 20 may trigger a stronger anticancer response. In this study, we found that L-Norvaline inhibits tumor growth in vivo. Pathway analysis based on RNA-seq data indicated that the differentially expressed genes (DEGs) were significantly enriched in some immune-related path-ways. Significantly, L-Norvaline did not inhibit tumor growth in immunodeficient mice. In addition, combination treat-ment with L-Norvaline and ADI-PEG 20 induced a more robust anti-tumor response against B16F10 melanoma. Furthermore, single-cell RNA-seq data demonstrated that the combination therapy increased tumor-infiltrating CD8+ T cells and CCR7+ dendritic cells. The increase in infiltrated dendritic cells may enhance the anti-tumor response of CD8+ cytotoxic T cells, indicating a potential mechanism for the observed anti-tumor effect of the combination treat-ment. In addition, populations of immunosuppressive-like immune cells, such as S100a8+ S100a9+ monocytes and Retnla+ Retnlg+ TAMs, in tumors were dramatically decreased. Importantly, mechanistic analysis indicated that the processes of the cell cycle, ribonucleoprotein complex biogenesis, and ribosome biogenesis were upregulated after combination treatment. This study implied the possibility of L-Norvaline as a modulator of the immune response in cancer and provided a new potential therapy combined with ADI-PEG 20.
    Date: 2023-05-30
    Relation: American Journal of Cancer Research. 2023 May 30;13(5):1952-1969.
    Link to: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244097/
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2156-6976&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001002130900019
    Appears in Collections:[Kwang-Yu Chang] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    ISI001002130900019.pdf9512KbAdobe PDF135View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback