Destroying CD163 Tumor Associated Macrophages Allows the Immune System to Better Attack a Cancer

Cancers tend to subvert portions of the immune system into aiding and protecting growth of tumors. The innate immune cells known as macrophages are involved in growth and regeneration, and populations of macrophages resident in tumors become a part of the cancer process. Some of these macrophages have clear surface markers, and can thus be targeted for destruction. Researchers here demonstrate that doing this allows the rest of the immune system to more aggressively attack a tumor. This class of approach may turn out to be quite effective when combined with other forms of immunotherapy that are focused on making T cells more aggressive and capable of destroying cancerous cells.

A new form of immunotherapy that has so far been tested on mice makes it probable that oncologists in the future may be able to treat some of the patients who are not responding to existing types of immunotherapy. Instead of attacking the cancer cells directly, the new technique target and remove a subtype of immune cells known as macrophages, after which the immune system begins to attack the cancer. "We've studied what happens to the tumour when it is exposed to targeted treatment that removes precisely ten per cent of the macrophages that are supporting the cancer tumour instead of fighting it. The most important result is that the depletion of this specific type of macrophage causes the tumour to shrink, which is triggered by a subsequent mobilisation of new macrophages and, ultimately, also an activation of T cells which attack the tumour."

The type of macrophages which the researchers have removed express a specific receptor, CD163, on the cell surface. Unlike other macrophages, these are known to have an undesirable effect in connection with cancer. Instead of recognising cancer cells as unwanted tissue, the macrophage sees the tumours as normal tissue that needs help with regeneration. It is also widely recognised that survival rates are worse if there are many macrophages that express the CD163 receptor in the tumour.

"Our study suggests that the macrophages we're hitting function as a kind of 'peacekeeping' force that keeps the 'attackers' away. When the peacekeeping macrophages in the tumour are removed, the attackers can instead be mobilised, after which the T cells and a number of other macrophages collaborate to attack the tumour. What is interesting is that the whole thing happens by itself as soon as we remove the tenth of the macrophages that express CD163, and that these appear to want to 'decide' which immune cells can be allowed to get into and out of the tumour."