Enhancing cancer immunotherapy Alzheimer's disease risk genes provide new targets

Scientists have found a new tool to boost cancer immunotherapy, according to a major study published online today in Cell, a leading academic journal.
found in many types of cancer, immune cells have a new potential therapeutic target.
the protein in mouse experiments, it releases the power of immunotherapy and completely removes the tumor.
note that some related antibodies have entered clinical trials as this new target has received great attention in the field of Alzheimer's treatment in recent years.
study was led by Professor Marco Colonna of the University of Washington School of Medicine.
immunologist, he has long focused on the relationship between immune cells in Alzheimer's disease.
the surface of a small glial cell, an immune cell in the brain, to express a subject, TREM2.
growing body of research suggests that mutations in the TREM2 gene can lead to poor performance of small glial cells that do not effectively remove brain "garbage" such as neurotoxic proteins.
the TREM2 gene variant is also thought to be a genetic factor that has a significant impact on the risk of Alzheimer's disease.
, the scientists note that treM2, in addition to appearing on small glial cells, also appears on another type of immune cell, macrophages.
and these macrophages are located inside the tumor.
when we looked at where TREM2 appeared, we found that they were expressed in large numbers inside the tumor, not outside the tumor."
"Professor Colonna said, "this means that it would be an ideal target because it would not affect the surrounding tissue when targeting TREM2."
" in a variety of types of cancer, tumor-soaked macrophages express TREM2 (Photo Source: Reference 1) Tumor-soaked macrophages promote an environment that inhibits T-cell activity.
so the team envisions whether inhibiting TREM2 can help reduce immunosuppression and increase the lethality of T-cells. To test this hypothesis, the researchers designed a set of experiments.
They injected cancer cells into mice to induce the development of sarcoma, and then divided the mice into four groups, allowing them to receive immunosuppressant anti-PD-1 antibodies, TREM2 antibodies, anti-PD-1 antibodies and TREM2 antibodies, and as a control of physiological saline.
the control group, sarcoma quickly grew larger and larger.
in mice treated with TREM2 antibodies or anti-PD-1 antibodies, tumors also grew slowly in most cases.
, however, all mice that received both antibodies showed encouraging results, with tumors starting to shrink after just 10 days and most of them disappearing completely in more than 20 days! In another group of mice injected with colorectal cancer cells, the combined use of antiTREM2 antibodies with immuno-checkpoint inhibitors also showed amazing tumor removal.
PD-1 inhibitors, in association with TREM2 antibodies, showed better anti-tumor effects than anti-PD-1 antibody monodride therapy (Photo Source: Reference 1) Further analysis of mice treated with TREM2 antibodies, and the researchers saw a real change in the immune cells in the tumor: a significant reduction in inhibitory macrophages, while T cells became abundant and active.
shows that blocking TREM2 is an effective way to enhance T-cell anti-tumor activity.
to confirm that their findings were clinically significant, the researchers assessed the relationship between TREM2 expression and clinical outcomes in cancer patients.
higher levels of TREM2 in colorectal and breast cancer are associated with shorter lifetimes, according to publicly available data from the U.S. Cancer Genetics Database.
study schematics (photo source: Resources1) Researchers say they are expanding TREM2 research to more types of cancer, using animal models to do more to validate the results.
is pleased that some antiTREM2 antibodies are already being used in clinical trials to treat other diseases.
, if these (animal models) work successfully, we can move relatively easily to clinical trials.
," Professor Colonna added.
References, (1) Martina Molgora et al., (2020) TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhanced Anti-PD-1 Immunotherapy. Cell. DOI: .2) Immunotherapy-resistant cancers eliminated in mouse study. Retrieved Aug. 12, 2020, from.