- Aug 3, 2021
A group of researchers at the Washington University School of Medicine in St. Louis has found that the effects of a standard immunotherapy drug to counter cancer could be enhanced by blocking the protein in TREM2.
The study was published in the journal Cell, and this could show a new way for cancer research.
“Essentially, we have found a new tool to enhance tumor immunotherapy,” said senior author Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology. “An antibody against TREM2 alone reduces the growth of certain tumors, and when we combine it with an immunotherapy drug, we see a total rejection of the tumor. The nice thing is that some anti-TREM2 antibodies are already in clinical trials for another disease. We have to do more work in animal models to verify these results, but if those work, we’d be able to move into clinical trials fairly easily because there are already a number of antibodies available.”
T cells have the ability to destroy tumor cells, but the tumors survive by forcefully creating a suppressive immune environment that subdues the T cells. Checkpoint inhibition has been used for ages to attack the tumor, but it always fell short of something and proved itself to being not enough when it comes to attacking the tumor. Colonna and Martina Malgora, Ph.D., a postdoctoral researcher, found that the same kind of immune cells, known as macrophages, were also found in tumors where they produce TREM2 and subdues T cells.
Colonna and Molgora along with colleagues Robert D. Schreiber, Ph.D., the Andrew M. and Jane M. Bursky Distinguished Professor; and William Vermi, MD, an immunologist at the University of Brescia tried to find out if the use of TREM2 could reduce immunosuppression and thereby enhance the ability of T cells to attack and kill tumors.
As part of the experiment, the researchers divided mice into four groups; in one group the mice received an antibody that blocked TREM2, the second group was given a checkpoint inhibitor, the third group was given both, and the fourth group was given a placebo. As for the mice who received the TREM2 or the checkpoint inhibitor alone, it turns out that the tumors grew very slowly, and in a few cases, the tumors completely disappeared.
In another research carried out by Ekaterina Esaulova, it was found that blocking TREM2 turned out to be an effective means of boosting T cell activity. This could be huge for cancer research as a whole since macrophages with TREM2 are found in many kinds of cancers.
The researchers will try to expand their TREM2 study into other kinds of cancers to see the results. As mentioned by Colonna, if their animal trial becomes successful, they will surely go into a clinical trial.