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    Home > Active Ingredient News > Antitumor Therapy > Nat Immunol: As a worker, the immune cells will be "exhausted". The Nature publication teaches you how to "resurrect T cells" and eliminate cancer!

    Nat Immunol: As a worker, the immune cells will be "exhausted". The Nature publication teaches you how to "resurrect T cells" and eliminate cancer!

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    Tumor is a systemic disease, and its treatment process requires long-term planning, like a marathon, but due to the long confrontation in this tug-of-war, the T cells that fight tumors are unable to do what they want
    .
    Therefore, in order to become a winner on the track and avoid the phenomenon of "T cell exhaustion", it is imperative to improve the defense power of cells on the road to slowly fighting cancer

    .

    Recently, scientists at the La Jolla Institute for Immunology (LJI) have found a breakthrough to solve this problem
    .
    They found that the basic leucine zipper transcription factor "BATF" cooperates with the interferon regulatory factor 4 "IRF4" to effectively combat T cell depletion in mouse tumor models

    .

    Related research BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells was published in Nature Immunology magazine
    .

    BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells Nature Immunology

    As the most important immune cell in the human immune system, T cells play an indispensable role in resisting bacterial viruses and other foreign pathogens and killing cancer cells
    .
    A large number of studies have found that the activation of CD8+ T cells requires the TCR-CD3 complex to receive the antigen information presented by the antigen-presenting cells, and it also requires costimulatory signals provided by a variety of accessory molecules to clear pathogen-infected cells and tumor cells.

    .

    On the contrary, if the costimulatory signal is lacking, the CD8+ T cells that infiltrate the tumor tissue for a long time will enter a state of "exhaustion or dysfunction", resulting in symptoms of immune incompetence and loss of anti-tumor ability
    .
    Therefore, even the most cutting-edge cancer immunotherapy "CAR-T therapy", there will be T cell failure

    .

    In fact, CD8+ T cell effects and depletion responses are both initiated by T cell receptor (TCR) signals, and nuclear factor of activated T cells (NFAT) is a type of transcription factor with multidirectional regulatory functions.
    Both play an important role

    .

    Therefore, in order to determine which transcription factor is more effective against cell failure, researchers transferred three NFAT-AP-1 active transcription factors "JUN, MAFF and BATF" into mouse models of melanoma and colorectal cancer, respectively.
    As a result, it was found that controlling the overexpression of BATF by CAR-T cells is beneficial to eliminate tumors without causing T cell exhaustion, and the long-term survival rate of mice has also been significantly improved

    .

    BATF-transduced CAR T cells exhibit enhanced tumor rejection

    BATF-transduced CAR T cells exhibit enhanced tumor rejection BATF-transduced CAR T cells exhibit enhanced tumor rejection

    Previous studies have shown that T cell depletion usually prevents T cells from producing a strong memory response to recurrent cancer.
    However, surprisingly, this latest study reverses the traditional view.
    The study pointed out that BATF-transduced CAR-T The cells will continue to exist after the tumor subsides and become the umbrella for the same tumor to attack the human body again

    .

    BATF-transduced CAR T cells persist after tumor regression

    BATF-transduced CAR T cells persist after tumor regression, BATF-transduced CAR T cells persist after tumor regression

    In order to more effectively combat the T cell exhaustion program, the researchers found in further experiments that the combination of BATF and interferon regulatory factor 4 (IRF4) has a better effect.
    It is well known that IRF4 is a transcription factor protein that is found in B cells, T cells and macrophages play an important role in the functions of macrophages.
    Studies have found that the combination of the two can not only improve the ability of T cells to fight fatigue, but also effectively improve the ability of T cells to fight tumors

    .

    BATF-IRF4 interaction is essential for anti-tumor response

    BATF-IRF4 interaction is critical for anti-tumor response BATF-IRF4 interaction is critical for anti-tumor response

    Patrick G.
    Hogan of the La Jolla Institute for Immunology (LJI), one of the authors of the study, said: "Cell therapy currently only shows extraordinary efficacy in blood diseases, while the development of solid tumors is still difficult

    .
    And BATF overexpression The law is a promising way to improve CAR-T therapy and combat solid tumors

    .
    "

    Original source:

    Original source:

    Seo, H.
    , González-Avalos, E.
    , Zhang, W.
    et al.
    BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells .
    Nat Immunol (2021).
    https://doi.
    org/10.
    1038/ s41590-021-00964-8.

    BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells

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