Cells from a patient with acute myeloid leukemia. Image credit: Lance Liotta laboratory (Public Domain)
The human immune system can recognize and kill cancer cells growing in the body. Certain immune cells recognize mutated proteins on the surface of cancer cells known as antigens, and this ability can be enhanced by drugs. These so-called immunotherapies can be effective to treat several cancer types, but only some patients benefit from them. This is because cancer cells often stop presenting antigens on their surface, thus hiding from the immune response.
Natural killer cells are a type of immune cell that does not rely on antigen presentation to recognize cancer cells. Scientists are now trying to develop drugs to increase the effectiveness with which natural killer cells attack cancer.
Pech et al. used cells from a human leukemia, a type of blood cancer, to look for proteins that made these cells more vulnerable to natural killer cells. The main experiment, in which every single protein in the cancer cells was deleted one by one, revealed that a protein called DCAF15 changes how cancer and natural killer cells interact. Leukemia cells lacking DCAF15 could be attacked by natural killer cells much more easily because the cancer cells exhibited inflammation-like symptoms that stimulated the immune response. DCAF15 is part of a family of ‘adaptors’ that that provide specificity to the cellular machinery that controls proliferation, the recycling of proteins and DNA repair.
Inhibiting DCAF15 with a drug also made natural killer cells more efficient at eliminating leukemia cells. Patients with leukemia whose cancer cells make little DCAF15 protein have a better chance of survival, suggesting that this process may already be happening in some patients.
Together these data indicate that targeting DCAF15 in leukemia patients may help natural killer cells attack cancer cells. Future research is needed to see if a similar process takes place in other cancer types.
