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    Current Topics Discussion #2

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    kaneeshka namasivayam
    Necroptosis, a form of programmed cell death, occurs in dying tumor cells surrounding areas of necrosis. Blocking necroptosis causes tumor cell death to shift to apoptosis instead. Necroptosis promotes tumor metastasis by suppressing the anti-tumor immune response of CD8 T cells and macrophages. Tumor cell necroptosis regulates the tumor microenvironment and inhibits cytotoxic CD8 T cell function, thereby increasing metastasis.

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    Current Topics Discussion #2

    Uploaded by

    kaneeshka namasivayam
    27 views21 pages
    Necroptosis, a form of programmed cell death, occurs in dying tumor cells surrounding areas of necrosis. Blocking necroptosis causes tumor cell death to shift to apoptosis instead. Necroptosis promotes tumor metastasis by suppressing the anti-tumor immune response of CD8 T cells and macrophages. Tumor cell necroptosis regulates the tumor microenvironment and inhibits cytotoxic CD8 T cell function, thereby increasing metastasis.

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    Necroptosis, a form of programmed cell death, occurs in dying tumor cells surrounding areas of necrosis. Blocking necroptosis causes tumor cell death to shift to apoptosis instead. Necroptosis promotes tumor metastasis by suppressing the anti-tumor immune response of CD8 T cells and macrophages. Tumor cell necroptosis regulates the tumor microenvironment and inhibits cytotoxic CD8 T cell function, thereby increasing metastasis.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    27 views21 pages

    Current Topics Discussion #2

    Uploaded by

    kaneeshka namasivayam
    Necroptosis, a form of programmed cell death, occurs in dying tumor cells surrounding areas of necrosis. Blocking necroptosis causes tumor cell death to shift to apoptosis instead. Necroptosis promotes tumor metastasis by suppressing the anti-tumor immune response of CD8 T cells and macrophages. Tumor cell necroptosis regulates the tumor microenvironment and inhibits cytotoxic CD8 T cell function, thereby increasing metastasis.

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 21

    Necroptosis, Tumor Necrosis and

    Metastasis
    TNF-induced necroptosis:
    Tumor necrosis Tumors with necrosis:
    Breast tumor
    Late stage tumor
    with necrosis
    More aggressive
    Metastasis
    More mortality
    Poor prognosis

    H&E staining : haemotoxylin and eosin

    http://oraclebio.com/portfolio-item/tumor-necrosis-morphology/
    1. Does necroptosis happens in cancer?
    2. Is necroptosis responsible for tumor necrosis?
    3. Does necroptosis regulate tumor metastasis and
    tumor microenvironment?
    Part 1-Cancer model

    MMTV-PyMT model: Vector: cDNA-Polyoma Virus middle T antigen + pMMTV(Mouse Mammary Tumor Virus)-SV40 vector
    & FVB/N zygotes

    Good model for


    breast cancer &
    metastasis

    Clin Cancer Res; 19(12) June 15, 2013


    Part 1-Tumor necrosis in MMTV-PyMT breast cancer
    Part 1-Necroptosis activation in MMTV-PyMT breast cancer

    aa b

    c
    Part 1-Necroptosis activation in MMTV-PyMT breast cancer
    Part 1-Necroptosis activation human breast cancer
    d
    c

    g
    e f
    Part 1-Necroptosis activation human lung and liver cancer
    1. Does necroptosis happens in cancer?
    2. Is necroptosis responsible for tumor necrosis?
    3. Does necroptosis regulate tumor metastasis and
    tumor microenvironment?
    Part 2-MLKL knockout breast cancer model: 2) MMTV-PyMT model
    Part 2-Tumor cell death in MLKL deficient breast cancer models
    Part 2-Remaining cell death in MLKL deficient tumor-Apoptosis

    Live cell Live cell


    Part 2-Remaining cell death in MLKL deficient tumor-Apoptosis
    1. Does necroptosis happens in cancer?
    2. Is necroptosis responsible for tumor necrosis?
    3. Does necroptosis regulate tumor metastasis and
    tumor microenvironment?
    Part 3-Tumor metastasis in MLKL deficient breast cancer models
    Part 3-Effects of tumor cell necroptosis on tumor-infiltrating immune cell
    population
    Part 3-Effects of tumor cell necroptosis on cytotoxic T lymphocytes (CTL) function

    Cytotoxic CD8 T cell: Granzyme B-direct tumor cell cytotoxicity


    IFN-gamma-immune regulation
    Part 3-Effects of CD8 T cell depletion on tumor metastasis in the presence/absence of necroptosis
    Summary

    1. Necroptosis activation happens in dying tumor cells around


    necrotic area

    2. Tumor cell necroptosis is responsible for tumor necrosis,


    necroptosis blockage shift tumor cell death to apoptosis

    3. Tumor cell necroptosis promotes tumor metastasis by suppressing


    CD8 T cell and macrophage functions

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