Last week some truly exciting work on new therapies for breast cancer patients was published in Science Translational Medicine. These results show how it might be possible in the near future to target immune checkpoints in breast cancer – a malignancy previously thought to be resistant to this type of therapy.
An immune checkpoint is a rather general term referring to a chemical signalling pathway that is used by the immune system to stop itself from attacking cells in the body. Immune cells are dangerous killing machines, primed to attach bacteria, fungi and parasites entering the body. In order to make sure they don’t turn on the body attack healthy cells, immune cells have pre-set biochemical mechanisms that stop them from “friendly fire”. However, these fail-safe mechanisms are only helpful when the danger is coming from outside the body – as in the case for bacterial or viral infections. In cancer, the danger is coming from within. Cancer cells display all the “safety flags” regular cells display, which is how they mostly are able to avoid the “immune checkpoints” and “fly under the radar” undetected by the immune system. Drugs that block these immune checkpoints have proved very successful in treating several different types of cancer – including lung cancer and melanoma – but have not proved very successful in treating breast cancer. A least, not yet. Exciting new work from researchers from the University of Melbourne, Australia has currently shed new light on new possibilities.
The main reason why immune checkpoint therapy is not usually very successful in breast cancer patients is that breast cancer cells usually carry a relatively small number of mutations. Immune therapy is most effective in tumors that are hypermutated – that is, tumors that carry a lot of mutations. While all tumors by definition carry several mutations some carry more than others, which is why for instance lung cancer is generally more responsive to this type of therapy than breast cancer. However, not all types of breast cancer are the same. Tumors that carry a BRCA-1 mutation, for example, tend to carry a much higher number of mutations that other types of breast cancer. What’s more, BRCA-1 mutated tumors tend to have a greater number of infiltrating immune cells (lymphocytes) – that is, immune cells that make their way deep into the tumor. It is therefore not surprising that in order to manipulate infiltrating tumor cells these tumor express high levels of immunomodulatory molecules PDCD1 and CTLA4. By using immune checkpoint inhibitor drugs, researchers were able to “wake up” the immune cells present throughout the tumor, which resulted in the immune system viciously attacking cancer cells. This immune therapy in combination with regular chemotherapy almost halter the progress of the tumor. These results have been tested in an animal model of BRCA-1 breast cancer: whether similar effects are going to be seen in human patients remains to be seen. However, these findings are incredibly promising, opening a new path of hope for patients with BRCA-1 mutated breast cancer.