2025 GIGA Annual Report | 25 THE IMPACT OF CHARCOT-LEYDEN CRYSTAL PROTEIN ON MESOTHELIOMA CHEMOTHERAPY: TARGETING EOSINOPHILS FOR ENHANCED CHEMOSENSITIVITY Willems M, Hamaidia M, Fontaine A, Grégoire M, Halkin L, Vilanova Mañá L, Terres R, Jamakhani M, Deshayes S, Brostaux Y, Heinen V, Louis R, Duysinx B, Jean D, Wasielewski E, Scherpereel A, Blanquart C, Willems L. . Mesothelioma (MPM) patients show poor outcomes, with clinical evidence linking eosinophil count to overall survival and chemotherapy response. Researchers from the Laboratory of Cellular and Molecular Epigenetics, led by Luc Willems, investigated the role of eosinophil-derived factors in mesothelioma response to chemotherapy. They found that eosinophil-conditioned supernatants inhibited apoptosis in mesothelioma cells exposed to cisplatin and pemetrexed, both in 2D cultures and spheroids. The anti-apoptotic effect involved interactions with Charcot-Leyden Crystal protein or Galectin-10 (CLC-P/Gal10), and recombinant CLC-P/ Gal10 mimicked this effect. In a preclinical mouse model, eosinophilia altered chemotherapy response, but not tumor growth. Pre-treatment with anti-Siglec-F antibody restored chemotherapy effectiveness. This study provides mechanistic insight into the link between eosinophils and poor mesothelioma outcomes, opening avenues for potential therapeutic strategies. EBioMedicine. 2024 Nov;109:105418. doi: 10.1016/j.ebiom.2024.105418. p LINKS | Publication on ORBI | Luc Willems
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