Researchers of the de Duve Institute have discovered how a broad variety of tumor cells block the function of human CD8 T cells, the killer cells of our immune system, by coating them with a protein that could be compared to some molecular glue. The study, which was led by Anne-Elisabeth Petit and Pierre van der Bruggen of the de Duve Institute and the Brussels Branch of the Ludwig Institute for Cancer Research, details how this glue—a naturally occurring protein named galectin—stops activated T cells that are primed and ready to kill cancer cells from triggering their attack.
Galectin is a protein produced at high levels by a broad range of cancer cells, including those from pancreatic, ovarian and colon tumors. Researchers of the de Duve Institute have previously shown that removing galectin from T cells with an antibody or other chemicals can turn lethargic T cells isolated from tumors into cancer cell-killing machines again.
The study has two significant clinical implications. On the one hand, it indicates that the method of assessing the function of tumor-infiltrating T cells—measuring the production of cytokines, not their release—is likely to provide false positives. On the other hand, it also suggests that drugs that counter galectin may potently boost immunotherapies that activate T cell responses, such as checkpoint blockade, which releases the breaks on T cell response.
The results were recently published in Nature Communications.
|Pierre van der Bruggen & Anne-Elisabeth Petit|
Anne-Elisabeth Petit, Nathalie Demotte, Benoît Scheid, Claude Wildmann, René Bigirimana, Monica Gordon-Alonso, Javier Carrasco, Salvatore Valitutti, Danièle Godelaine & Pierre van der Bruggen. A major secretory defect of tumour-infiltrating T lymphocytes due to galectin impairing LFA-1-mediated synapse completion. Nature Communications 7, 12242 (2016).