“Ancient origins of tumor-host interactions: insights from the Drosophila model.” The Bilder Lab (University of Berkeley, USA) studies the molecules and mechanisms that govern the polarity, growth, and morphogenesis of epithelia, the fundamental tissue of all animals and the major constituent of human organs. They also use Drosophila cancer models as a simple system to understand both how epithelial organization prevents tumor formation and how tumors actually kill their hosts. Example of recent work: Bilder et al., Tumour-host interactions through the lens of Drosophila, Nature Reviews Cancer (2021) There is a large gap between the deep understanding of mechanisms driving tumour growth and the reasons why patients ultimately die of cancer. It is now appreciated that interactions between the tumour and surrounding non-tumour (sometimes referred to as host) cells play critical roles in mortality as well as tumour progression, but much remains unknown about the underlying molecular mechanisms, especially those that act beyond the tumour microenvironment. Drosophila has a track record of high-impact discoveries about cell-autonomous growth regulation, and is well suited to now probe mysteries of tumour – host interactions. Here, we review current knowledge about how fly tumours interact with microenvironmental stroma, circulating innate immune cells and distant organs to influence disease progression. We also discuss reciprocal regulation between tumours and host physiology, with a particular focus on paraneoplasias. The fly’s simplicity along with the ability to study lethality directly provide an opportunity to shed new light on how cancer actually kills.

This workshop will explore cancer from an evolutionary perspective, with a strong focus on how cancer appeared and evolved and on the different forms of cancer across taxa. Speakers This workshop will gather the best world-leading experts on this issue: David Bilder (Berkeley, USA) Thomas Bosch (Kiel, Germany) James DeGregori (University of Colorado, USA) Mathieu Giraudeau (CNRS, La Rochelle, France) Vera Gorbunova (Rochester, USA) Crisanto Gutierez (Madrid, Spain) Hanna Kokko (Zürich, Switzerland) Carlo Maley (Arizona State University, USA) Elizabeth Murchison (Cambridge University, United Kingdom) Samir Okasha (University of Bristol, United Kingdom) Joshua D. Schiffman (University of Utah, USA) Flash talks – Bertrand Daignan-Fornier (IBGC, CNRS, Bordeaux, France) – Lucie Laplane (IHPST & Gustave Roussy, Paris, France) – Maël Lemoine (ImmunoConcept, University of Bordeaux, France) & Thomas Pradeu (ImmunoConcept, CNRS, France) – Benjamin Spada (ImmunoConcept, CNRS, France) Organizers – Bertrand Daignan-Fornier (IBGC, CNRS, Bordeaux, France) – Mathieu Giraudeau (LIENSs, CNRS, La Rochelle, France) – Thomas Pradeu (ImmunoConcept, CNRS, France) – Benjamin Spada (ImmunoConcept, CNRS, France) Venue Hôtel de la Plage, Arcachon, France 10, Avenue Nelly Deganne 33120 Arcachon, Tel. +33 (0)5 56 83 06 23; email: infos@hotelarcachon.com Further information : https://www.philinbiomed.org/event/arcachon-cancer-and-evolution/

Role of extracellular vesicles in and DNA sensing in the activation anti-tumor immune responses induced by targeted radiotherapy. Resume: Dr. Jean-Pierre Pouget is an INSERM director of research with a renowned expertise in the development of novel radiotherapeutic approaches to treat cancer. He directs the laboratory of “Radiobiology for Targeted and Personalized Radiotherapy” at the IRCM in Montpellier. Together with Dr. Julie Constanzo they developed and optimized a novel radiotherapy approach for cancer called targeted radionuclide therapy (TRT). TRT consists of a delivery of low-dose radiation over long periods of time by the administration of a radiolabeled antibodies targeting specific molecules expressed on tumors (antigens). This approach allows a specific irradiation of tumor cells that overexpress the targeted antigen, while minimizing exposure of healthy tissues. Interestingly, they show that this approach efficiently eliminates established tumors, but to do so it requires a fully functional immune system. Indeed, such TRT approach boosts the establishment of antitumor immune responses and protects immunocompetent hosts from secondary tumor challenge. Mechanistically, TRT contribute to the secretion of exosomes by tumors which are responsible for the activation of anti-tumor immune responses. Accordingly, vaccination with exosomes originating from TRT treated tumor cells delays tumor growth in vivo while the inhibition of exosome formation in vivo reduced the therapeutic potential of TRT. The activation of the immune system by TRT is likely due to the DNA present within exosomes inducing the production of type I interferons upon its sensing by innate immune DNA sensor cyclic GMP-AMP synthase (cGAS). Therefore, the team of Jean-Pierre Pouget has developed a novel radiotherapy approach targeting both tumor cells and stimulating anti-tumor immune responses that hold great promise in the treatment of cancer patients.