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"Bernard, Vincent"
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Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.
Journal Article
Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity
Although B cell response is frequently found in cancer, there is little evidence that it alters tumor development or progression. The process through which tumor-associated antigens trigger humoral response is not well delineated. We investigate the repertoire of antigens associated with humoral immune response in pancreatic ductal adenocarcinoma (PDAC) using in-depth proteomic profiling of immunoglobulin-bound proteins from PDAC patient plasmas and identify tumor antigens that induce antibody response together with exosome hallmark proteins. Additional profiling of PDAC cell-derived exosomes reveals significant overlap in their protein content with immunoglobulin-bound proteins in PDAC plasmas, and significant autoantibody reactivity is observed between PDAC cell-derived exosomes and patient plasmas compared to healthy controls. Importantly, PDAC-derived exosomes induce a dose-dependent inhibition of PDAC serum-mediated complement-dependent cytotoxicity towards cancer cells. In summary, we provide evidence that exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity.
The humoral immune response role in cancer is unclear. Here the authors perform an in-depth proteomic profiling of immunoglobulin-bound proteins in plasma from pancreatic ductal adenocarcinoma patients and find cancer-cell specific antibodies neutralized by binding to cancer-cell derived exosomes.
Journal Article
Grace of Monaco : Princess in Dior
A singular look into Grace of Monaco's stylish life through the exceptional dresses that the house of Dior created for her over the years. Grace Kelly's life may have transformed from that of a Hollywood star to Princess of Monaco, but her status as a style icon remained constant throughout her life. There is perhaps no better record of this than her close thirty-year-long relationship with the illustrious house of Dior. Published on the occasion of the 2019 exhibition at the Musâee Christian Dior in Granville, France, this sophisticated illustrated volume celebrates the close collaboration between Grace Kelly and the artistic directors of Dior throughout the years, from Christian Dior, to her support of Yves Saint Laurent, and her close friendship with Marc Bohan. An in-depth overview of this special exhibition, this new title explores the evolving relationship between Dior's designers and their muse through insights from experts on Dior and Monaco's royals--including an intimate interview with Princess Grace's favorite couturier and close friend, Marc Bohan--and beautiful images from Dior's archives as well as an exclusive photoshoot in Monaco. Fashion-loving readers will be delighted to rediscover the classic elegance of Grace Kelly's wardrobe through the gorgeous designs created for her by Dior.
BOOK
Conflict in Syria: Finding hope amid the ruins
Humanity has been undergoing a trial of fire and blood in Syria since 2011. What is happening? Over time, this conflict has exhibited all possible guises of war: civil war, proxy war, siege warfare, cyber-warfare and war against terror. All forms of past and present warfare seem to converge in this one conflict. A war against children, against hospitals, against cities, against first-aid workers, against memory, against justice – maybe these are more accurate titles for this war.Whatever names we give it, we can attempt to grasp the enormity of this tragedy with some figures and orders of magnitude. Although there is no widespread agreement on the number of dead, a New York Times article published in April 2018 puts the most widely accepted death count at 470,000.1 According to a UNICEF report, as of March 2018, around 30,000 people were wounded per month, 1.5 million were living with a permanent handicap, 6.5 million were suffering from food shortages, and 70% of the population was living in extreme poverty. 1.75 million children were not able to attend school, with one out of every three schools unfit for use owing to the war.2More than 11 million people, or around half of the pre-war population, have been uprooted from their homes. Some 5 million people have had to flee the country, and 13.5 million rely on humanitarian assistance to survive.3 Most of the country's infrastructure has been destroyed, the economy has collapsed, the country's health-care system – among the best in the region before the war – has imploded, and entire cities and neighbourhoods have been reduced to vast ruins.
Journal Article