Fight Aging!

It remains the case that far too much of the extensively funded work on cancer therapies is only relevant to a tiny subset of cancers. This is no way to achieve success in the fight to control cancer: there is only so much funding, only so many researchers, and too many types of cancer for an incremental strategy to make earnest process over the next few decades. The important lines of research into cancer treatments are those that can in principle be applied to many (or preferably all) cancers, and that are in principle highly effective, such as inhibition of telomere lengthening. The ideal cancer therapy is one that can be delivered systemically throughout the body, and will effectively destroy any and all cancers that it encounters. That therapy could then be mass manufactured, at costs crushed down by the logistics of scale, and given to all cancer patients.

Immunotherapy has revolutionized cancer treatment by stimulating the patient's own immune system to attack cancer cells, yielding remarkably quick and complete remission in some cases. But such drugs work for less than a quarter of patients because tumors are notoriously adept at evading immune assault. Now a new study has found that the effects of a standard immunotherapy drug can be enhanced by blocking the protein TREM2, resulting in complete elimination of tumors. "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."

T cells, a kind of immune cell, have the ability to detect and destroy tumor cells. To survive, tumors create a suppressive immune environment in and around themselves that keeps T cells subdued. A type of immunotherapy known as checkpoint inhibition 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. A protein called TREM2 is associated with underperforming immune cells in the brain in the context of Alzheimer's disease. Researchers realized that the same kind of immune cells, known as macrophages, are found in tumors, where they produce TREM2 and promote an environment that suppresses the activity of T cells.

Researchers injected cancerous cells into mice to induce the development of a sarcoma. The mice were divided into four groups. In one group, the mice received an antibody that blocked TREM2; in another group, a checkpoint inhibitor; in the third group, both; and the fourth group, placebo. In the mice that received only placebo, the sarcomas grew steadily. In the mice that received the TREM2 antibody or the checkpoint inhibitor alone, the tumors grew more slowly and plateaued or, in a few cases, disappeared. But all of the mice that received both antibodies rejected the tumors completely. 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. Further experiments revealed that macrophages with TREM2 are found in many kinds of cancers.

Link: https://medicine.wustl.edu/news/immunotherapy-resistant-cancers-eliminated-in-mouse-study/