Amazing! Cell: Blocking TREM2 enhances tumor immunotherapy and completely removes tumors from mouse models.

The emergence of immunotherapy has revolutionized cancer treatment.
, however, current immunotherapy drugs are only effective in less than a quarter of patients.
because tumors are too "sly", cancer cells suppress their immunogenic characteristics and induce a microencase to actively suppress the immune response in order to evade Immune surveillance of T cells.
, how do cancer cells suppress the immune response? It turns out that it directly affects T cell response by introducing immuno checkpoints such as cytotoxic T lymphocyte-related antigen-4 (CTLA-4) and programmed death-1 (PD-1).
checkpoint inhibitors effectively "wake up" T-cells and begin to attack tumors.
, checkpoint suppression alone may not be sufficient to eliminate tumors when the tumor environment still has immunosuppressive effects.
further studies have found that tumors also actively inhibit anti-tumor T-cell responses by absorbing bone marrow cells.
is an important cell component in many tumor micro-environments and inhibits T-cell response through a variety of mechanisms.
is considered to inhibit cells, recent studies have shown that tumor-soaked bone marrow cells are quite heterogeneic and may actually include immunostatulation and immunosuppression subsexuals.
Therefore, removing inhibited myelin cells from tumors, blocking their function, or inducing myelin cells with immunostification properties may be an important way to improve immunotherapy strategies and may be used in collaboration with immunosupergent inhibitors.
's thinking is clear, and now researchers need to find "candidates."
August 12, in a paper published in the journal Cell, researchers at the University of Washington noticed TREM2, a myelin-cell-like body responsible for transmitting in-cell signals.
previous studies have found that TREM2 maintains the response of small glial cells to neurodegenerative lesions, such as Alzheimer's disease.
, TREM2 is also expressed by tumor-soaked macrophages.
the latest study, researchers found treM2 to be the perfect "target" because TREM2 is really expressed in large amounts within the tumor, which means that targeting TREM2 does not affect surrounding tissue.
this in mouse experiments, which enhance the role of PD-1 antibodies by blocking the TREM2 protein, which completely removes tumors in mice.
specifically, the team first demonstrated that tumors transplanted in mice lacking TREM2 grew more slowly.
further analysis showed that in these animals, CD8-T cells were more effective on tumors and may also respond more effectively to PD-1 checkpoint inhibitors.
researchers then conducted a study to examine the effects of direct blocking of TREM2 on tumor growth in mice.
injected cancer cells into mice to induce sarcoma.
then divided the mice into four treatment groups.
group accepted monoclonal antibodies (mAb) that block TREM2.
the second group received checkpoint inhibitors, the third group was treated with a combination of antiTREM2 antibodies and checkpoint inhibitors, and the fourth group was a control group, receiving a placebo.
results confirmed stable growth in sarcoma in mice receiving a placebo.
in animals that received only TREM2 antibodies or checkpoint inhibitors, tumors also grew slowly in most cases.
, all mice that received both antibodies began to have their tumors shrink after just 10 days, and most of them disappeared completely in more than 20 days.
researchers repeated the experiment using colorectal cancer cells, with similar results.
researchers analyzed immune cells in mouse tumors treated with TREM2 antibodies alone.
found that inhibitory macrophages were largely missing and T-cells were abundant and active.
shows that blocking TREM2 is an effective way to enhance the anti-tumor activity of T cells.
further experiments have shown that macrophages with TREM2 have been found in a variety of cancers.
to assess the relationship between TREM2 expression and clinical outcomes, the researchers turned to the Cancer Genome Map, a cancer genetic database jointly maintained by the National Cancer Institute and the National Human Genome Institute.
found that higher TREM2 levels were associated with shorter lifetimes in colorectal cancer (CRC) and triple-negative breast cancer (TNBC).
analysis of the database suggests that antiTREM2 therapy may be particularly promising in CRC and TNBC because TREM2 expression is negatively associated with the overall survival and recurrence of these cancer patients," the researchers said.
, can TREM2 be extended to other types of cancer? Through extensive pathological studies of human tumors, the researchers suggest that TREM2 may be a particularly attractive therapeutic target because it is highly expressed in the vast majority of the more than 200 primary and metastasis tumors examined.
, TREM2 is not highly expressed in normal organizations.
means that remodeling tumor-related macrophages with antiTREM2 mAb is a promising way to aid checkpoint immunotherapy.
next step, researchers will use human antibodies to model animals and, if all goes well, will continue to advance clinical trials.
we look forward to an early advance in this approach to clinical outcomes for the benefit of more cancer patients.
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