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    Home > Active Ingredient News > Immunology News > Sci Immuno iNKT cells help fight cancer

    Sci Immuno iNKT cells help fight cancer

    • Last Update: 2022-09-22
    • Source: Internet
    • Author: User
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    Written by My girlfriend Old Red Riding Hood


    Tumor-specific T cell-based immunotherapy has a significant effect in intervening in solid tumor metastasis [1].


    It works in such a way that lymphocytes infiltrated at the lesion can be modified and expanded in vitro into tumor antigen-specific T cells and then transfused back into the same patient
    .

    This therapy is particularly effective for melanoma, but has limited efficacy for adenocarcinomas because the former is rich in tumor invasive T cells and the latter is relatively low
    .

    This limitation can be achieved by genetically modifying T cells, such as T cell receptors or chimeric antigen receptors[2], but whether it is tumor-infiltrating T lymphocytes produced by itself or genetically modified T cells, tumor microenvironment support is required to completely eliminate tumor cells [3,4].


    The tumor microenvironment is a complex class of environments that contain stromal and immune cells, and usually have the effect of promoting tumor growth and inhibiting the immune response [5,6
    ].

    For most tumor types, the tumor microenvironment is rich in myeloid cells, such as monocytes, macrophages, dendritic cells, and their precursors
    .

    They work synergistically to regulate the immune response [7, 8
    ].

    In general, inflammatory macrophages (i.
    e.
    , M1 macrophages) and dendritic cells have anti-tumor effects, while tissue repair macrophages (i.
    e.
    , M2 macrophages) and myeloid precursor cells have pro-tumor effects
    .

    Therefore, the underlying concept of immunotherapy should be to target immune cells
    with pro-tumor effects.
    CD1d-restricted invariant natural killer T (iNKT) that recognizes CD1d is a highly conserved subtype of T cells that, although rare in number, plays a fairly important role
    in defending against mouse and human solid tumors.

    iNKT cells can directly kill tumor cells
    expressing CD1d.

    In addition, it can also play an anti-tumor effect
    by promoting the expression of inflammatory phenotypes and immune activation phenotypes of immune cells.

    Activation of iNKT cells can be achieved by injecting the CD1d agonist-GalCer, which promotes the expression of IFN-r and co-stimulating molecules, thereby activating dendritic cells as well as downstream anti-tumor CD8+ T cells and NK cells
    .

    Of course, -GalCer relies on cell-based vaccines or nanocarriers to enter the body to function
    .

    In 2022, the Giulia Casorati and Paolo Dellabona research group from Milan, Italy, presented a presentation in Science Immunology titled TCR-engineered iNKT cells induce robust antitumor response by dual targeting cancer and The suppressive myeloid cells article provides an in-depth study
    of the anti-tumor effects and mechanisms of iNKT cells.

    First, the authors engineered the T cell receptor of iNKT cells to OT-I TCR iNKT, whose T cell receptor specifically recognizes the SIINFEKL polypeptide of MHC-I, which is a widely distributed tumor-specific antigen
    .

    Next, the authors examined the recognition of CD1d- and MHC-I-specific antigens by the engineered cells
    .

    By co-culturing with melanoma cell lines, the authors determined that the modified iNKT has antigen bispecificity and can effectively target tumor cells
    expressing tumor antigens in vitro.
    Further down, the authors investigated whether the engineered iNKT cells had an inhibitory effect
    on tumor development in vivo.

    The authors transposed a mixture of OT-I TCR iNKT cells and iNKT cells into mice and found that OT-I TCR iNKT cells had a stronger anti-tumor effect than traditional iNKT cells and T cell receptor-modified cells, and the authors speculated that the authors speculated that it may be because of the dual targeting effect of OT-I TCR iNKT cells, that is, targeting both tumor cells and myeloid cells
    .
    Finally, the authors validate
    the above guess.

    The authors transposed OT-I TCR iNKT cells into mice and detected tumor-infiltrating lymphocytes by methods such as flow cytometry
    .

    The authors determined that OT-I TCR iNKT cells can directly target tumor cells
    .

    At the same time, OT-I TCR iNKT cells can also act on myeloid cells in the tumor microenvironment, prompting them to be in an inflammatory state, thereby further improving the anti-tumor effect
    .
    In addition, the authors injected GalCer-MSV, an agonist of microparticle-assembled OT-I TCR iNKT cells, into mice, and determined that GalCer was similar to the transfusion of OT-I TCR iNKT cells, which could effectively inhibit tumor development
    .

    The two-pronged approach is even more
    effective.
    In summary, the authors determined that OT-I TCR iNKT cells genetically modified with T cell receptors can play an antitumor role
    .

    The mechanism is because it can target tumor-specific antigens and play an effective killing effect on tumors; It can also act on the tumor microenvironment and activate the anti-tumor response
    of the myeloid cell population.
    The source of the article is https://doi.
    org/10.
    1126/sciimmunol.
    abn6563


    Model Maker: Eleven

    References


    1.
    E.
    Tran, P.
    F.
    Robbins, S.
    A.
    Rosenberg, ‘Final common pathway’ of human cancer immunotherapy: Targeting random somatic mutations.
     Nat.
    Immunol.
     18, 255–262 (2017).

    2.
    C.
    H.
    June, M.
    Sadelain, Chimeric antigen receptor therapy.
     N.
    Engl.
    J.
    Med.
     379, 64–73 (2018).

    3.
    W.
    A.
    Lim, C.
    H.
    June, The principles of engineering immune cells to treat cancer.
     Cell 168, 724–740 (2017).

    4.
    K.
    Gowrishankar, L.
    Birtwistle, K.
    Micklethwaite, Manipulating the tumor microenvironment by adoptive cell transfer of CAR T-cells.
     Mamm.
    Genome 29, 739–756 (2018).

    5.
    S.
    A.
    Rosenberg, Cell transfer immunotherapy for metastatic solid cancer-what clinicians need to know.
     Nat.
    Rev.
    Clin.
    Oncol.
     8, 577–585 (2011).

    6.
    T.
    Kitamura, B.
    Z.
    Qian, J.
    W.
    Pollard, Immune cell promotion of metastasis.
     Nat.
    Rev.
    Immunol.
     15, 73–86 (2015).

    7.
    A.
    Mantovani, F.
    Marchesi, A.
    Malesci, L.
    Laghi, P.
    Allavena, Tumour-associated macrophages as treatment targets in oncology.
     Nat.
    Rev.
    Clin.
    Oncol.
     14, 399–416 (2017).

    8.
    H.
    Salmon, R.
    Remark, S.
    Gnjatic, M.
    Merad, Host tissue determinants of tumour immunity.
     Nat.
    Rev.
    Cancer 19, 215–227 (2019).

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