Researchers have discovered a protein that acts as a brake on natural killer cells, and they show how removing it enhanced mice’s ability to fight lethal forms of cancer. They suggest the finding could lead to new cancer immunotherapies – treatments that boost the patient’s own immune system to fight disease.
The researchers, including Dr. Nicholas Huntington, who heads a molecular immunology lab at the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia, describe their discovery in the journal Nature Immunology.
Natural killer (NK) cells are specialized white blood cells in the innate immune system – the body’s frontline defense system. They guard against tumors and launch attacks against infections.
Dr. Huntington says developing a cancer immunotherapy from their findings would entail “learning how to activate the NK cells of the individual patient and boost their immune system to tackle the disease.”
NK cells are constantly searching for and eliminating cells that pose a threat. If this process is disrupted, then the rogue cells escape and can give rise to disease or a tumor.
NK cells are controlled by signaling proteins called cytokines that activate or inhibit them. One of these is a cytokine called Interleukin 15 (IL-15), which activates NK cells.
In their study, the researchers found a protein inside NK cells that acts like a “brake” on the cell by reducing its response to IL-15.
The protein is called CIS – short for “cytokine-inducible SH2-containing protein.”
When they deleted the gene that codes for the CIS protein, the researchers found it made the NK cells hypersensitive to IL-15.
In various mouse models of cancer, the researchers found that silencing both copies of the animals’ gene for CIS prevented melanoma, prostate, and breast cancers becoming metastatic (spreading to other parts of the body).
The researchers note their findings identify a powerful switch inside NK cells that enhances the body’s ability to tackle tumors and “suggest possibilities for new cancer immunotherapies directed at blocking CIS function.”
“We are hopeful our research will lead to new immunotherapies that supercharge the body’s natural killer cells, and maintain it in a highly active state to more efficiently and specifically fight cancer.”
Dr. Nicholas Huntington