Cell: Completely eliminate the tumor! Inhibition of this protein can greatly enhance the effectiveness of immunotherapy.

T-cells, as important immune cells in the human body, have the ability to detect and destroy tumor cells, but tumors can create an inhibitory immune environment in and around themselves, thus maintaining T-cells in an inhibited state.
, researchers at Washington University School of Medicine in St. Louis recently found in mice that blocking the TREM2 protein enhances the effectiveness of standard immunotherapy drugs and even eliminates tumors alnough.
the study may shed light on potential new ways to make immunotherapy effective for more cancer patients.
The study, published August 11 in the journal Cell, is entitled "TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhanced Anti-PD-1 Immunotherapy", and pathology professors Dr. Marco Colonna and Dr. Robert Rock Bellive, said, "In essence, we have found new tools to enhance tumor immunotherapy.
antibodies to TREM2 alone reduce the growth of certain tumors, and when we use them in association with immunotherapy drugs, we see tumors completely rejected.
, some anti-TREM2 antibodies have entered clinical trials for another disease.
we have to do more in animal models to validate these results, and if they work, we will be able to enter clinical trials fairly easily, because there are a lot of antibodies available at the moment," he said.
" immune cells soak human tumors (Photo: William Vermi / Martina Molgora) T-cells are immune cells that have the ability to detect and destroy tumor cells.
but in order to survive, tumors create an inhibitory immune environment inside and around them, keeping T cells inhibited.
an immunotherapy called checkpoint suppression wakes T cells from the inhibition state so they can start attacking tumors.
but if the tumor environment is still immunosuppressive, checkpoint suppression alone may not be sufficient to eliminate the tumor.
As an expert on the immune system, Professor Colonna has long studied a protein called TREM2, which is linked to Alzheimer's disease, which is associated with poor performance of immune cells in the brain.
Colonna and lead author, postdoctoral researcher Dr Martina Molgora, realized that the same immune cells, called macrophages, were found in tumors, producing TREM2 in tumors and promoting an environment that inhibits T-cell activity.
look at the position of TREM2 in the body, we found that it expresses at a high level inside the tumor, not outside the tumor," said Colonna, a 13-year-old.
therefore, it is actually an ideal target, because if THEM2 is targeted, there is little impact on the external weekly organization.
Colonna and Molgora, together with Dr. Robert D. Schreiber, Andrew M. and Professor Jane M. Bursky, immunologists and M.D., of the University of Brescia, have joined forces to explore whether inhibition of TREM2 can reduce immunosuppression and enhance the lethality of T-cells.
as part of the study, researchers injected cancer cells into mice to induce the development of sarcoma.
mice were divided into four groups.
in one group, mice received antibodies that blocked TREM2.
received one checkpoint inhibitor in the other group, both in the third group, and a placebo in the fourth group.
mice that received only TREM2 antibodies or checkpoint inhibitors, tumors grew slower and tended to stagnate, disappearing in rare cases.
but all mice that received both antibodies completely rejected the tumor.
the researchers repeated the experiment using a colorectal cancer cell line, and the results were equally surprising.
abstract of the illustration, with the help of Ekaterina Esaulova, a graduate student working in the laboratory of Dr. Maxim Artyomov, associate professor of pathology and immunology, the researchers analyzed immune cells in mouse tumors treated only with TREM2 antibodies.
they found that inhibitory macrophages were missing in large numbers and 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 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 Atlas, a public database of cancer genetics maintained by the U.S. National Cancer Institute and the U.S. National Human Genome Institute.
they found that higher levels of TREM2 were associated with reduced survival in patients with colorectal and breast cancer.
, researchers are expanding their research into TREM2 to other types of cancer to see if inhibiting TREM2 is a potential strategy to fight cancer.
Molgora said: "We found TREM2 expressed in more than 200 human cancers and different subsysms, but we only tested models of colon, sarcoma and breast cancer, so there are other models that need to be tested."
addition, we have a mouse model with human TREM2.
," Colonna added, "the next step is to use human antibodies to build animal models."
it works, I think we can start clinical trials, " he said.
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