AACR: Little Vesicles Full of Hope
“For several years, we have known that cells secrete into their environment membrane vesicles called extracellular vesicles, that act as intercellular messengers”, explains Clotilde Théry, Inserm director of research and specialist in cell emanations. Since their discovery, these little vesicles have given rise to great hope for scientists. They are able to target cells, providing data to enable them to change, the basis for any targeted therapy. They have also been described as possible biomarkers, which can either boost or suppress the immune system, explaining why a whole session was devoted to these small cell vesicles at the largest American congress on cancer research.
Promising Cell Messengers
Everything is not so simple in the world of extracellular vesicles. A great variety of them exist and their composition affects their function. Their nature may differ greatly from one cell-type to another, making them possible biomarkers. Sometimes however, subtly different vesicles may be produced by the same cell, triggering different consequences. The Exosomes and Tumor Growth team (Inserm/Institut Curie), led by Clotilde Théry in the Cancer Immunotherapy Centre is helping to understand this issue. “Fifteen years ago, we conducted the first analyses on the composition of vesicles shed by dendritic cells, the famous sentinels of the immune system that warn when danger is identified”, explains the scientist. To date, we distinguish several major families, the most famous of which, exosomes, belong to the smallest of the vesicles.” Scientists from Institut Curie and Gustave Roussy discovered ten years ago that the exosomes secreted by dendritic cells carry specific marks and participate in triggering immune responses. By depositing a specific tumor marker (antigen) on these exosomes, they were even able to trigger an antitumor immune response. These results served as the basis for a phase II clinical trial, between Gustave Roussy and Institut Curie, on patients suffering from lung cancer.
Spotlight on Small Vesicles
Extracellular vesicles are now the object of much research. The AACR Congress is an opportunity to take stock of the latest progress in this field. One of the key elements presented by Clotilde Théry during her introductory speech was that “when we want to analyze the role of these vesicles in a pathological system, we need to know clearly whether what we are observing is specific to one vesicle or present in other vesicles.” The answer to this question will widen the possible scope of these messengers, specifically making them effective and reliable circulating biomarkers. While initial avenues have already described them as possible indicators of the presence of a cancer, namely pancreatic, further studies are required. For their therapeutic use, Clotilde Théry’s team have demonstrated that other vesicles than exosomes could also be used in clinical trials similar to the previous one.
The next step will be to understand how these vesicles produced by tumor cells modulate the immune system in one way or another. These vesicles seem to be able to stimulate or inhibit the immune system, opening up therapeutic possibilities. Clotilde Théry insisted on the need to pursue studies into the biology of these vesicles to understand how they form and are secreted to then be able to use them for therapeutic purposes. Other presentations in this session dealt with monitoring these vesicles and their possible role in metastatic dissemination. Expectations are high around these vesicles, explaining why many are keeping a close eye on them.