Much like Jedis, a certain type of immune cell trains itself to learn how to more effectively defend the body against cancer and infection, as was discovered by a team from the IRCM (Institut de recherches cliniques de Montréal) led by André Veillette, MD, in an article published in Nature Immunology. This 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,” says 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 defences by educating themselves through a series of molecular reactions,” explains 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,” adds Ning Wu.
Towards a therapeutic approach for cancer and infections
Now knowing that NK cells improve their defences through learning, Dr. Veillette 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,” reports 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.”
About the study
Dr. Veillette’s 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).
About André Veillette
André Veillette obtained his medical degree from the Université Laval. He is Full IRCM Research Professor and Director of the Molecular Oncology research unit. Dr. Veillette is also full research professor in the Department of Medicine (accreditation in molecular biology) at the Université de Montréal and adjunct professor in the Department of Medicine (Division of Experimental Medicine) at McGill University. Dr. Veillette holds the Canada Research Chair in Immune System Signalling.
About the IRCM
The IRCM (Institut de recherches cliniques de Montréal) is a renowned biomedical research institute located in the heart of Montréal's university district. Founded in 1967, it is currently comprised of 35 research units and four research specialized clinics: nutrition, metabolism and atherosclerosis; hypertension; diabetes; and rare diseases such as cystic fibrosis and familial hyperlipidemia. The IRCM employs nearly 425 people. It is affiliated with the Université de Montréal, and the IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). It also maintains a long-standing association with McGill University. The IRCM is funded by the Quebec ministry of Economy, Science and Innovation (Ministère de l’Économie, de la Science et de l’Innovation). For more information, visit www.ircm.qc.ca.