Highlight Publication March 2009

Aurore Saudemont, Fabien Garçon, Hakim Yadi, Marta Roche-Molina, Nayoung Kim, Anne Segonds-Pichon, Alfonso Martín-Fontecha, Klaus Okkenhaug, and Francesco Colucci (2009).
p110γ and p110δ isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease.
Proceedings of the National Academy of Sciences of the United States of America 106 5795-5800
http://dx.doi.org/10.1073/pnas.0808594106

Lay summary

White blood cells are made in the bone marrow and circulate throughout the body. The circulation throughout the body is regulated by various factors called chemokines. Understanding how these factors work is key to our appreciation of immune defences and efforts to redirect the trafficking of white blood cells in conditions such as cancer and inflammatory diseases. Molecules belonging to the family of phosphoinositide-3 kinases (PI3K) act within the cells to regulate movement towards different chemokines produced in distinct parts of the body. Among these molecules one in particular, PI3K p110γ, was thought to be the chief regulator of cell movement.

Natural Killer (NK) cells are a class of white blood cells found in the blood, lymph glands and tissues such as the liver, the lungs and the uterus, where they participate in immune defences against infection and cancer, as well as in reproductive success and in transplantation. Using a combination of genetics, imaging techniques and pharmacological approaches we have discovered that, unexpectedly, p110γ regulates only some aspects of NK cell trafficking, whereas p110δ - another member of the PI3K family - plays more dominant roles in directing NK cell migration to sites of inflammation, tumour growth and to the uterus during pregnancy.

Clinical trials are being carried out on new drugs which, by interfering with PI3K molecules, are expected to alleviate cancer and unwanted inflammation. Our work, published in the Proceedings of the National Academy of Sciences, adds important new information as to what the outcome of interfering with these molecules might be on the trafficking of NK cells and their versatile functions in health and disease. This in turn may help to design safe and effective new therapeutic approaches for treating cancer and inflammation. The work was funded by Cancer Research UK and BBSRC and carried out at the Babraham Institute by the groups of Francesco Colucci and Klaus Okkenhaug, in collaboration with Alfonso Martin-Fontecha of King’s College, London.

Current work in our laboratory aims to understand the mechanisms of NK cell trafficking in cancer and pregnancy and to explore the possibility of targeting PI3K to improve transplantation.

About the lead author:

Aurore Saudemont joined Francesco Colucci’s group at Babraham in 2005 after completing a PhD at Lille University and a postdoctoral training at the Memorial Sloan Kettering Institute, New York, studying cancer immunotherapy. Aurore’s work at Babraham has contributed to the understanding of NK cell activation and has opened new avenues for research in cancer and transplantation.