作者: Audemard, Corentin ; de Gassart, Aude ; Bergot, Elise ; Agaugué, Sophie ; Magrini, Elena ; Boucherit, Nicolas ; Louche, Pauline ; Gorvel, Laurent ; Kerneur, Clément ; Audebert, Stéphane ; Le, Kieu-Suong ; Rouvière, Marie-Sarah ; Carnevale, Silvia ; Cano, Carla E ; Drapeau, Marion ; Guillén Casas, Jaime ; Foucher, Etienne ; Fullana, Marie ; Garlanda, Cecilia ; Madakamutil, Loui ; Cano, Carla E. ; Colazet, Magali ; Olive, Daniel ; Mantovani, Alberto

Tumor-associated macrophages (TAMs), often adopting an immunosuppressive M2-like phenotype, correlate with unfavorable cancer outcomes. Our investigation unveiled elevated expression of the butyrophilin (BTN)2A1 in M2-like TAMs across diverse cancer types. We developed anti-BTN2A1 monoclonal antibodies (mAbs), and notably, one clone demonstrated a robust inhibitory effect on M2-like macrophage differentiation, inducing a shift toward an M1-like phenotype both in vitro and ex vivo in TAMs from patients with cancer. Macrophages treated with this anti-BTN2A1 mAb exhibited enhanced support for T cell proliferation and interferon-gamma (IFNγ) secretion. Mechanistically, BTN2A1 engagement induced spleen tyrosine kinase (SYK) recruitment, leading to sequential SYK and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibition of SYK or ERK phosphorylation abolished M2 reprogramming upon BTN2A1 engagement. Our findings, derived from an analysis of macrophages from healthy donors and human tumors, underscore the pivotal role of BTN2A1 in immunosuppressive macrophage differentiation and function, offering potential applications in cancer immunotherapy.

2024-09-01·European Journal of Cancer

Precision cancer medicine platform trials: Concepts and design of AcSé-ESMART

Review

作者: Berlanga, Pablo ; Marshall, Lynley V ; Bautista, Francisco ; Rubino, Jonathan ; Nysom, Karsten ; André, Nicolas ; Ducassou, Stephane ; Casanova, Michela ; Buzyn, Agnes ; Paoletti, Xavier ; Zwaan, C Michel ; Geoerger, Birgit ; Gatz, Susanne A ; Rubio-San-Simón, Alba ; Archambaud, Baptiste ; Marchais, Antonin ; Hoog-Labouret, Natalie ; Vassal, Gilles ; Blanc, Patricia ; Pellegrino, Sophie

Precision cancer medicine brought the promise of improving outcomes for patients with cancer. High-throughput molecular profiling of tumors at treatment failure aims to direct a patient to a treatment matched to the tumor profile. In this way, improved outcome has been achieved in a small number of patients whose tumors exhibit unique targetable oncogenic drivers. Most cancers, however, contain multiple genetic alterations belonging to and of various hallmarks of cancer; for most of these alterations, there is limited knowledge on the level of evidence, their hierarchical roles in oncogenicity, and utility as biomarkers for response to targeted treatment(s). We developed a proof-of-concept trial that explores new treatment strategies in a molecularly-enriched tumor-agnostic, pediatric population. The evaluation of novel agents, including first-in-child molecules, alone or in combination, is guided by the available understanding of or hypotheses for the mechanisms of action of the diverse cancer events. Main objectives are: to determine 1) recommended phase 2 doses, 2) activity signals to provide the basis for disease specific development, and 3) to define new predictive biomarkers. Here we outline concepts, rationales and designs applied in the European AcSé-ESMART trial and highlight the feasibility but also complexity and challenges of such innovative platform trials.

2024-09-01·Nature Cell Biology

A guideline on the molecular ecosystem regulating ferroptosis

Review

作者: Schick, Joel ; Sankaran, Vijay G ; Janowitz, Tobias ; Dai, Enyong ; Tang, Daolin ; Ran, Qitao ; Yang, Wan Seok ; Krautwald, Stefan ; Chi, Jen-Tsan ; Gabrilovich, Dmitry I ; Krysko, Dmitri V ; Adolph, Timon E ; Li, Changfeng ; Zhu, Xiaofeng ; Zhang, Donna D ; Bush, Ashley I ; Kagan, Valerian E ; Linkermann, Andreas ; Xie, Yangchun ; Greten, Florian R ; Bayir, Hülya ; Li, Binghui ; Garcia-Saez, Ana J ; Klionsky, Daniel J ; Karin, Michael ; Ichijo, Hidenori ; Kang, Rui ; Lotze, Michael T ; Jiang, Xuejun ; Chen, Xin ; Melino, Gerry ; Wang, Jiayi ; Zou, Weiping ; Baehrecke, Eric H ; Gan, Boyi ; Zeh, Herbert J ; Kroemer, Guido ; Liu, Jiao ; Yang, Minghua ; Toyokuni, Shinya ; Kopf, Manfred ; Stockwell, Brent R ; Galluzzi, Lorenzo ; Gu, Wei ; Ioannou, Maria S ; Liu, Jinbao ; Iovanna, Juan ; Yi, Qing

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

项与 Centre de Recherche en Cancérologie de Marseille 相关的新闻（医药）

2024-10-21

·PRNewswire

Okomera Gets €1.5 Million Grant to Develop Microfluidics & AI Powered CRISPR Editing Platform for Target Validation

PARIS, Oct. 21, 2024 /PRNewswire/ -- Okomera announces Bpifrance funding to develop and standardize novel CRISPR screening assay to accelerate drug discovery in oncology with leading cancer research center of Marseille, CRCM. Okomera is developing desktop platform for automated organoid screening using droplet-microfluidics and AI to accelerate drug discovery. Their patented tech developed after 10 years of research at Pasteur Institute and Ecole Polytechnique, provides Multiplexing, Co-culture and High-throughput screening of drug candidates on miniaturized Patient Derived Organoids (PDOs). Continue Reading Raphael Tomasi, CTO & Co-Founder of Okomera "We are honored to receive this grant from Bpifrance," said Sidarth Radjou, CEO of Okomera. Dr. Thomas Miller, Principal Investigator at IPC and CRCM, emphasized the significance of this collaboration: "This partnership is an extraordinary opportunity to advance our understanding of cancer biology. By developing and standardizing a CRISPR screening assay that can be directly applied to PDOs, we can create more accurate disease models. This will not only improve our ability to study cancer mechanisms but also enhance our capability to identify new therapeutic targets and develop more effective treatments." "We are thrilled to embark on this collaboration, as it offers an unprecedented opportunity to leverage cutting-edge technologies in cancer research," said Dr. Geraldine Guasch, Research Director Inserm at CRCM and Scientific Director of the 3D-HUB-O organoid platform. "By integrating CRISPR technology with Okomera's advanced organoid screening platform, we are setting the stage for more precise and effective therapeutic strategies. This project represents a significant step forward in translating scientific discoveries into tangible clinical applications, ultimately bringing us closer to improving outcomes for cancer patients." Corentin Molson, representing Bpifrance, commented: "Bpifrance is proud to support Okomera in this pioneering effort. Their innovative approach to developing and standardizing CRISPR screening on PDOs reflects our commitment to fostering innovation in healthcare. This project has the potential to make significant contributions to the field of precision medicine and improve outcomes for cancer patients." We would also like to recognize the contribution and assistance provided by AstraZeneca to support the successful grant application. About Okomera, visit our website: Paoli-Calmettes Institute: Based in Marseilles, Paoli-Calmettes Institute (IPC) is the first cancer comprehensive centre in region providing global care for cancer. It is a member of the national federation Unicancer. Further information: Photo - Logo - Contact: Sidarth Radjou, CEO [email protected] SOURCE Okomera WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED