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    Home > Active Ingredient News > Antitumor Therapy > Science Advances: Cancer cells are masters of hypnotism?

    Science Advances: Cancer cells are masters of hypnotism?

    • Last Update: 2022-05-21
    • Source: Internet
    • Author: User
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    In our impression, cancer cells are like a vicious thug, but in fact, the life of cancer cells is not easy, and they are always facing the siege from the immune system
    .
    In order to escape the pursuit of the immune system, cancer cells do everything possible to reduce the expression of MHC molecules that present antigens, hide themselves, or express immunosuppressive molecules such as PD-L1 to inhibit the activity of killer T cells

    .

    However, a new study from the University of Ottawa has discovered a new ability of cancer cells - "hypnotic" NK cells, blood cancer cells will transfer the cell membrane with PD-1 to NK cells, making them "dormant" ” state, thereby inhibiting their anticancer activity
    .

    To "hypnotize" NK cells, blood cancer cells transfer their membranes with PD-1 to NK cells, causing them to enter a "dormant" state, thereby inhibiting their anticancer activity
    .

    Recently, the study was published in Science Advances under the title: When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer .

    When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer Science Advances

    The fight against cancer is a battlefield without gunpowder smoke.
    If cancer cells are ferocious enemies, then natural killer (NK) cells are the sharp sword of the human immune system

    .
    However, overactivated NK cells can also damage the body, and NK cells are often inhibited by immune checkpoints, such as the PD-1/PD-L1 pathway

    .

    PD-1/PD-L1 immune checkpoint blockade therapy is one of the most effective immunotherapies at present
    .
    But what is puzzling is that NK cells, as special cancer killers, do not express PD-1 themselves, so how does the PD-1/PD-L1 pathway inhibit its activity?

    PD-1/PD-L1

    PD-1/PD-L1

    In this latest study, the research team found that a type of contact between cells, trogocytosis, can explain this doubt
    .
    Cytognathism means that lymphocytes gnaw off a part of the cell membrane from the antigen-presenting cell through the immune synapse, and this part of the cell membrane usually carries the cell membrane surface molecules of the donor cell, such as PD-1

    .

    Cytognathism leads to the transfer of PD-1 from tumor cells to NK cells

    Cytognathism leads to the transfer of PD-1 from tumor cells to NK cells

    In a mouse model of leukemia, the research team found that cytotoxicity between lymphocytes and tumor cells is very frequent, which also causes NK cells and CD8+ T cells to acquire PD-1 from leukemia cells
    .
    This also explains why NK cells do not express PD-1, but can be inhibited by the PD-1/PD-L1 pathway

    .

    Intratumoral lymphocytes acquire PD-1 from tumor cells in a leukocyte mouse model

    Intratumoral lymphocytes acquire PD-1 from tumor cells in a leukocyte mouse model

    From this point of view, the NK cell is not only a ruthless "killer" but also a "thief" - stealing the cell membranes carrying surface protein molecules from other blood cells
    .
    At present, scientists are not very clear about the function of cytognath, which may play a role in the induction and regulation of immune responses

    .
    But for cancer cells, cytotoxicity is undoubtedly a powerful weapon against immunotherapy

    .

    In patients with clonal plasma cell disease, the researchers confirmed by immunohistochemistry the cytotoxic effect of NK cells on blood cancer cells—not only PD-1 but also tumor cell markers
    .

    PD-1 and CD138 are also present in NK cells from patients with clonal plasmacytosis

    PD-1 and CD138 are also present in NK cells from patients with clonal plasmacytosis

    Michele Ardolino, Ph.
    D.
    , the corresponding author of the study and an assistant professor at the University of Ottawa, said that this study is not the missing link, allowing us to know where the PD-1 of NK cells comes from, although NK cells do not produce PD-1.
    , but they steal from cancer cells

    .
    While it's unclear why they do this, it's clear that cancer cells take advantage of this, causing NK cells to go dormant and elude the immune system

    .

    Altogether, this study elucidates a novel mechanism for regulating NK cell function by acquiring PD-1 from tumor cells
    .
    The discovery of this mechanism solves the mystery of how PD-1 inhibitors act on NK cells, and a better understanding of how these drugs act on different kinds of immune cells may guide novel immunotherapies for cancer
    .

    This study elucidates a novel mechanism for regulating NK cell function by acquiring PD-1 from tumor cells
    .

    Original source:

    Original Source: Original Source:

    MOHAMED S.
    HASIM, et al.
    When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer.
    SCIENCE ADVANCES, 13 Apr 2022, Vol 8, Issue 15.

    MOHAMED S.
    HASIM, et al.
    When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer.
    SCIENCE ADVANCES, 13 Apr 2022, Vol 8, Issue 15.


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