Immunotherapy is considered as a major breakthrough in cancer treatment. In some cases, it has achieved remarkable success. However, immunotherapy-based cancer treatment is not effective in almost 75% of cancer patients. This is because cancer cells discover new ways to avoid immune assault.
A new study in mice, conducted by researchers at Washington University has generated fresh hopes for an effective immunotherapy drug. In the mice model, they have shown that such drug can be successful if TREM2 protein is blocked. Blocking the protein may even result in complete elimination of tumors.
The findings have been published in the journal Cell.
“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 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.”
How do cancer cells avoid T cells, which have the power to identify cancer cells? With the help of drugs, T cells, a kind of immune cells, can also, destroy cancer cells.
Tumors know how to subdue T cells, and make them less effective. Immunotherapy fails in such cases when tumors create a suppressive immune environment to protect itself from any immune assault.
Checkpoint inhibition is one of the immunotherapy treatments, which has been able to achieve only partial success. It wakes T cells from their quiescence so they can begin attacking the tumor. But if the tumor environment is still immunosuppressive, checkpoint inhibition alone may not be enough to eliminate the tumor.
One of the researchers, involved in the current study, has long studied a protein called TREM2 in the context of Alzheimer’s disease.
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Marco Colonna, who has been doing research on Alzheimer’s disease, found a common immune cell, known as macrophages, in both the diseases. Like in Alzheimer’s disease, macrophages also produces TREM2 in cancer patient. This promotes an environment that suppresses the activity of T cells.
The current research has found that targeting TREM2 is not a difficult task. The researchers found that inside the tumor, TREM2 is expressed at its highest levels. So targeting TREM2 will have little side effects on non-cancerous tissue.
In order to induce the development of a sarcoma, the researchers divided mice into four groups. Tumors grew very slowly in mice groups which received either the TREM 2 or the checkpoint inhibitor. Tumor disappeared completely in mice groups which received both antibodies: TREM2 antibody and the checkpoint inhibitor.
The researchers repeated the experiment using a colorectal cancer cell line with similarly impressive results.
The researchers analyzed immune cells in the tumors of the mice treated with the TREM2 antibody alone. They found that suppressive macrophages were largely missing and that T cells were plentiful and active, indicating that blocking TREM2 is an effective means of boosting anti-tumor T cell activity.