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    Home > Active Ingredient News > Antitumor Therapy > Nature Communications: An anti-cancer weapon from intestinal bacteria that enhances the effect of CAR-T through anti-tumor metabolites

    Nature Communications: An anti-cancer weapon from intestinal bacteria that enhances the effect of CAR-T through anti-tumor metabolites

    • Last Update: 2021-08-02
    • Source: Internet
    • Author: User
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    The intestinal flora is a collection of large numbers of bacteria in the human intestine
    .


    It is estimated that each person’s digestive tract carries approximately 100 trillion bacteria from thousands of species


    In recent years, the intestinal flora has been a research hotspot
    .


    More and more discoveries indicate that the intestinal flora is not only of core importance for digestion, but also affects a large number of bodily functions


    Recent studies have shown that the intestinal flora can directly affect the effect of cancer immunotherapy
    .


    However, there is very little research on the role of intestinal flora metabolites in regulating cancer immunotherapy


    July 1, 2021,German research team at the University of Nature Communications journal published a report entitled: Microbial catena alberghiera Short-fatty Acids modulate CD8 + T and the Cell Responses Improve adoptive Immunotherapy for Cancer research paper
    .

    Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer

    This study is the first experiment to prove that the two microbial metabolites of valeric acid and butyric acid enhance the anti-tumor activity of immune cells through metabolism and epigenetic reprogramming, confirming that valeric acid and butyric acid have optimal effects in cancer immunotherapy
    .

    Symbiotic bacteria containing broad-spectrum enzymes can produce a variety of small molecules that can be used for therapeutic intervention
    .


    The research team observed that the low-abundance human symbiont M.


    They then treated CD8 + T cells with supernatant containing valeric acid and butyric acid from M.
    massiliensis to observe their functional changes
    .


    The results showed that valeric acid and butyric acid produced by M.


    Short-chain fatty acids (SCFA) are known inhibitors of histone deacetylase (HDAC) that can modulate the fate of eukaryotic cells through epigenetic methods
    .

    The research team compared the histone deacetylase (HDAC) inhibitory activity of the supernatants from 16 species of human symbiotic bacteria
    .


    They found that butyrate and valerate inhibit HDAC class I enzymes, reprogram CD8 + T cells, and increase the production of pro-inflammatory and cytotoxic molecules


    Further experimental results show that treatment with fatty acid valerate enhances the ability of tumor-specific T cells against solid tumor models
    .

    Normal T cells are "blind" to tumor cells to a large extent, while CAR-T cells can recognize specific target antigens on the tumor surface and kill cancer cells
    .


    Therefore, in order to further develop potential treatment strategies, the research team studied the impact of short-chain fatty acids (SCFA) on CAR-T cell therapy


    They found that valerate treatment enhanced the therapeutic effect of CAR-T cell therapy on pancreatic cancer, proving the potential of using valeric acid and butyric acid to optimize CAR-T cell generation to enhance CAR-T cell adoptive transfer.


    In summary, the study revealed two microbial metabolites valeric acid and butyric acid that can be used to enhance cellular anti-tumor immunity, and demonstrated two potential anti-tumor therapies: one is the use of valeric acid and butyric acid to optimize cytotoxic T cells The other is to transfer the bacterial population that produces these short-chain fatty acids (SCFA) to patients receiving adoptive cell therapy


    Original source:

    Original source:

    Luu, M.
    , Riester, Z.
    , Baldrich, A.
    et al.
    Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer.
    Nat Commun 12, 4077 (2021).
    https://doi.
    org/10.
    1038/s41467-021-24331-1.

    Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer.
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