Australian researchers have uncovered a new checkpoint protein that hampers natural killer (NK) cell-mediated tumor immunity. The findings, showing that depleting this protein in mice renders them resistant to a number of solid cancers by “switching on” NK cell activity, was recently published in Nature Immunology under the title “CIS is a potent checkpoint in NK-cell mediated tumor immunity.”
NK cells are effector lymphocytes that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage.
“Natural killer cells are a key part of our immune system that locate other cells posing a danger to health either because they are infected or because they are becoming a cancer cell,” Dr. Sandra Nicholson, one of the study’s lead authors, said in a press release.
The identification of immune checkpoints, such as the programmed cell death protein 1 (PD-1), whose inhibition removes the brakes of cytotoxic T-cells, has markedly improved cancer outcomes, particularly in metastatic melanoma. Now, researchers have identified a new checkpoint within NK cells that controls their ability to identify and attack tumor cells.
The activity of NK cells is mediated, among other signals, by cytokines such as IL-12, IL-18, and IL-15. The research team, led by Nicholson and Dr. Nicholas Huntington, with their colleagues from the Queensland Institute of Medical Research, has uncovered a protein named CIS that suppresses the NK cells’ ability to respond to IL-15, thereby hampering their ability to attack cancer cells.
Interestingly, when the investigators genetically engineered mice to lack Cish, the gene that coded for CIS, they found that the animals were resistant to experimental tumor metastasis derived from melanoma, breast cancer, and prostate cell lines, and this was dependent on NK activity.
“This is about learning how to activate the NK cells of the individual patient and boost their immune system to tackle the disease,” Huntington said.
The researchers believe that therapeutic inhibition of CIS in patients with certain cancers may improve patients prognosis by augmenting the activity of NK cells.
“We are hopeful our research will lead to new immunotherapies that supercharge the body’s natural killer cell, and maintain it in a highly active state to more efficiently and specifically fight cancer,” Huntington added.