Natural killer cells improve defenses through learning: study

Montreal, QC – A team of researchers from the IRCM (Institut de recherches cliniques de Montréal) have discovered a type of immune cell that trains itself to learn how to more effectively defend the body against cancer and infection. The team, led by André Veillette, recently published an article about the discovery in Nature Immunology.

The discovery could lead to the development of certain cancer treatments and to a better understanding of a rare disease, the X-linked lymphoproliferative (XLP) syndrome, also known as Duncan’s syndrome.

The natural killer (NK) cells’ main function is to protect the body by eliminating cancer and virus-infected cells. “Due to this feature, NK cells are already being used in treatments to control leukemia,” said Dr. Veillette. “As part of this research, our group sought to understand how to increase NK cell activity in order to take greater advantage of this therapeutic property.”

After 10 years of research, the team was able to conclude that NK cells develop the ability to defend themselves over time. “Just like a student learning in school, NK cells learn to improve their defenses by educating themselves through a series of molecular reactions,” said Ning Wu, associate researcher in André Veillette’s group and first author of the article. This mechanism involves three molecules: the SLAMF6 receptor, the SAP adaptor and an enzyme named SHP-1. “As the education occurs, NK cells learn to more effectively eliminate harmful cells,” added Dr. Wu.

Now knowing that NK cells improve their defenses through learning, Dr. Veillette said he hopes to pave the way for the development of innovative therapies against cancer and certain viral infections.

The discovered mechanism could also contribute to a better understanding of Duncan’s syndrome. This rare disease, also known as the XLP syndrome, affects only young boys and occurs when they come into contact with the Epstein-Barr virus, which causes mononucleosis. It is estimated that, without treatment, 70 per cent of patients with Duncan’s syndrome die before they reach the age of 10.

“Our research group had previously shown that the SAP adaptor does not react normally in patients with XLP syndrome,” said Dr. Veillette. “Therefore, NK cells are unable to kill infected cells. Now that we know that SAP interacts with the SLAMF6 receptor and the SHP-1 enzyme, we hope to clarify what leads to the onset of Duncan’s syndrome.”

The research was funded by the Canadian Institutes of Health Research, the China-Canada Joint Health Research Initiative, the Canadian Cancer Society Research Institute, the Fonds de recherche du Québec – Santé and the Canada Research Chairs program. The project was conducted at the IRCM by Ning Wu, Ming-Chao Zhong, Romain Roncagalli, Luis-Alberto Pérez-Quintero, Huaijian Guo, Zhanguang Zhang, Zhongjun Dong and André Veillette, in collaboration with Sylvain Latour and Christelle Lenoir, of the Institut Imagine in Paris (France). Zhongjun Dong is now at Tsinghua University in Beijing (China).