IMMUNOTHERAPY

NATURAL KILLER (NK) CELLS

14 million new cancer cases a year 8.2 million cancer deaths were reported in 2012. These shocking statistics show that cancer is a huge problem facing modern society. However, there is hope on the horizon with the promising development of new immunotherapeutic drugs. Immunotherapy is a treatment that uses the patient’s own immune system with added man-made components to target cancers. Immunotherapeutic drugs make up one quarter of the total 374 experimental cancer drugs currently on the pipeline. There are currently two types of immunotherapies being researched or trialed. The first type targets solid tumors such as lung cancers. The second type focuses on modifying immune cells to combat blood malignancies.

NK cells are best known for killing virally infected cells, and detecting and controlling early signs of cancer. As well as protecting against disease, specialized NK cells are also found in the placenta and may play an important role in pregnancy. NK cells were first noticed for their ability to kill tumour cells without any priming or prior activation (in contrast to cytotoxic T cells, which need priming by antigen presenting cells). They are named for this ‘natural’ killing. Additionally, NK cells secrete cytokines such as IFNγ and TNFα, which act on other immune cells like Macrophage and Dendritic cells to enhance the immune response.

​

While on patrol NK cells constantly contact other cells. Whether or not the NK cell kills these cells depends on a balance of signals from activating receptors and inhibitory receptors on the NK cell surface. Activating receptors recognize molecules that are expressed on the surface of cancer cells and infected  cells, and ‘switch on’ the NK cell. Inhibitory receptors act as a check on NK cell killing. Most normal healthy cells express MHC I receptors which mark these cells as ‘self’. Inhibitory receptors on the surface of the NK cell recognise cognate MHC I, and this ‘switches off’ the NK cell, preventing it from killing. Cancer cells and infected cells often lose their MHC I, leaving them vulnerable to NK cell killing. Once the decision is made to kill, the NK cell releases cytotoxic granules containing perforin and granzymes, which leads to lysis of the target cell.  

​

Because of their ability to kill tumour cells, NK cells are an attractive target for cancer immunotherapies. Some therapeutic monoclonal antibodies rely on NK cell killing. Researchers are also developing treatments to activate NK cells using small molecules or cytokines, and even testing genetically modified living NK cells as therapies.