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    Home > Active Ingredient News > Antitumor Therapy > Nat Commun: CAR-T cells enhance the efficacy of immunotherapy by mediating the depletion of macrophages associated with immunosuppressive tumors

    Nat Commun: CAR-T cells enhance the efficacy of immunotherapy by mediating the depletion of macrophages associated with immunosuppressive tumors

    • Last Update: 2021-02-24
    • Source: Internet
    • Author: User
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    Immunosuppressive tumor micro-environment (TME) is the main obstacle to the effective response of tumor-specific T cells to cancer.
    Tumor-related macrophages (TMAs) are the main components of TME, consisting of esophageal, transcription, and functionally distinct groups of highly heterogeneic and malleable macrophages that can support tumor growth through a variety of mechanisms, including secretion growth factors, substrogen degradation enzymes, and angiogenesic factors.
    , however, because macrophages are an integral part of the innocular immune system, some pan-macrophage treatments may cause systemic toxicity and/or inflammatory reactions.
    , it is particularly important to develop more effective drugs and programmes that can be applied clinically.
    FR beta in TAMEs for ovarian cancer expresses that the current next-generation treatment strategies, including CAR-T (embedded antigen-subject T cells), can reprogram TME.
    as an alternative to CAR-T therapy, which directly targets cancer cells, targeting TME non-tumor components has become an indirect treatment to limit tumor development.
    FR beta (folic acid β) is a glyphosate inositol-anchored subject expressed in acute myeloid leukemia cells and has been targeted by tumor antigens for CAR-T cell therapy.
    study, which targets TAMS with high expression of FR beta in ovarian cancer, the researchers confirmed that TAM, which expresses FR beta, has immunosuppressive M2 characteristics.
    In the mouse model of the same tumor, the selective elimination of FR beta-TAM in CAR-T cell-mediated TME leads to the accumulation of inflammatory monocytes, the influx of endogenetic tumor-specific CD8-T cells, which ultimately inhibits tumor development and prolongs survival time.
    same time, pre-treatment of TME by FR beta-specific CAR-T cells can also improve the effect of tumor-oriented anti-mesotrene CAR-T cells, while using both CAR-T cells at the same time does not produce the corresponding effect.
    in summary, the results reveal the tumor-promoting effects of FR beta-TAM in TME and the therapeutic significance of drugs targeted at eliminating TAM as preparation aids for conventional immunotherapy that directly target tumor antigens.
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