Cancers subvert the immune system in order to protect themselves while they grow. One of the ways in which this happens is activities of macrophage cells that become associated with the tumor tissue. Cancer cells influence the macrophages into dampening the local immune response, preventing the immune system from effectively targeting the tumor. Researchers here find a way to reduce the impact of this process, and note that it synergizes well with the currently popular checkpoint inhibitor approach to rousing the immune system to attack cancerous cells.
One reason behind many unsuccessful cancer treatments is the cancers' ability to hijack the immune system to support its own growth. This is assisted by the so-called tumour-associated macrophages that can be educated by cancer cells to dampen anti-tumour immune responses. Macrophages are phagocytes that form the first line of defence towards invading pathogens and they have a crucial role in maintaining tissue homeostasis. Macrophages have a large repertoire of functions in immune activation and resolving inflammation.
Researchers investigated the possibility to utilise tumour-associated macrophages to increase the immunological detection and killing of cancer cells. Previously, it was observed that Clever-1 controls leukocyte trafficking between tissues. A new study found that blocking Clever-1 function on macrophages activated the immune system and was highly effective in inhibiting cancer progression. By inhibiting Clever-1 functions, tumour-associated macrophages that normally impair adaptive immune cell activation, such as cancer cell killing by cytotoxic T cells, were managed to be re-educated so that they had increased ability to present antigen and secrete pro-inflammatory cytokines leading to increased activation of killer T cells.
The antibody therapy targeting Clever-1 worked in the studied tumour mouse models as efficiently as the PD-1 antibody therapy that is in clinical use. The PD-1 antibody maintains the functionality of the killer T cells. It is notable that the Clever-1 antibody therapy targeting macrophages also increased the activity of the killer T cells efficiently. In certain mouse models of cancer, a combination of anti-Clever-1 and anti-PD-1 therapies prevented tumour growth and formation of metastases more effectively than either treatment alone.