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    Home > Medical News > Medical World News > PD-1 antibody combined with TREM2 inhibitor Mouse tumor completely subsides!

    PD-1 antibody combined with TREM2 inhibitor Mouse tumor completely subsides!

    • Last Update: 2020-09-10
    • Source: Internet
    • Author: User
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    Text . . . In order to evade the surveillance of the immune system, cancer cells weaken their immunogenic characteristics and induce inhibitory immunologic microencases inside and around them to suppress the response of T cells.
    Although immuno-checkpoint inhibitors can awaken silent T-cells to attack tumors, if immunosuppressive effects in the tumor microencase persist, the use of checkpoint inhibitors may not be sufficient to eliminate tumors.
    a new study published in Cell on August 11th, researchers at the University of Washington School of Medicine completely eliminated tumors in mice by blocking the TREM2 protein to enhance the role of PD-1 antibodies.
    findings point to a new combination therapy that could allow more cancer patients to benefit better from immunotherapy.
    Photo Source: Cell co-author Professor Marco Colonna, an expert in the field of immune systems, has long focused on the role of TREM2 protein, a myelin-like subject, in Alzheimer's disease and has found that TREM2 is associated with poor performance of immune cells in the brain.
    and studies have shown that macrophages in tumors can also produce TREM2 and promote an environment that inhibits T-cell activity.
    Colonna team observed that high levels of TREM2 expression occur inside the tumor rather than outside the tumor, which means that treatment targeting TREM2 has little effect on surrounding tissue, indicating that TREM2 is an ideal target.
    they then set out to determine whether inhibiting TREM2 expression could reduce immunosuppression and enhance the lethality of T-cells.
    researchers injected cancer cells into mice to induce sarcoma formation, then divided the mice into four groups and received TREM2 antibodies, PD-1 antibodies, TREM2 antibodies and PD-1 antibodies, and a placebo.
    results showed stable growth of sarcoma in mice receiving only a placebo; tumors in mice receiving only TREM2 antibodies or PD-1 antibodies grew more slowly and were stable, with only a few mice disappearing; but all mouse tumors that received both TREM2 antibodies and PD-1 antibodies disappeared altogether.
    repeated experiments in colorectal cancer cells also showed amazing tumor removal.
    TREM2 antibody-enhanced PD-1 antibody-induced tumor subsides (Photo: Cell) After analyzing mouse tumors treated with TREM2 antibodies only, the researchers found a large number of inhibitory macrophages missing, while T-cells were abundant and active, suggesting that blocking TREM2 was an effective way to enhance anti-tumor T-cell activity.
    further experiments have shown that macrophages expressing TREM2 are present in a variety of cancers.
    the relationship between TREM2 expression and clinical outcomes, the researchers found that higher levels of TREM2 in colorectal and breast cancer were associated with shorter lifetimes.
    TREM2 is associated with poor prognosis (Photo: Cell) In fact, TREM2 is expressed in more than 200 human cancers and different subsypes, but the study only tested models of colorectal, sarcoma and breast cancer.
    researchers are now extending TREM2 research to other types of cancers to see if inhibiting TREM2 expression in these cancers is a promising treatment strategy.
    Colonna said that if further animal model studies were successful, they would advance the clinical development of TREM2 antibodies.
    reference: 1 s Martina Molgora et al. TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhanced Anti-PD-1 Immunotherapy. Cell (2020) 2 - Immunotherapy-resistant cancers eliminated in mouse study (Source: Medical Xpress)
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