Details

Autor(en) / Beteiligte

• Nguyen, Marie
• De Ninno, Adele
• Mencattini, Arianna
• Mermet-Meillon, Fanny
• Fornabaio, Giulia
• Evans, Sophia S.
• Cossutta, Mélissande
• Khira, Yasmine
• Han, Weijing
• Sirven, Philémon
• Pelon, Floriane
• Di Giuseppe, Davide
• Bertani, Francesca Romana
• Gerardino, Annamaria
• Yamada, Ayako
• Descroix, Stéphanie
• Soumelis, Vassili
• Mechta-Grigoriou, Fatima
• Zalcman, Gérard
• Camonis, Jacques
• Martinelli, Eugenio
• Businaro, Luca
• Parrini, Maria Carla

Titel

Dissecting Effects of Anti-cancer Drugs and Cancer-Associated Fibroblasts by On-Chip Reconstitution of Immunocompetent Tumor Microenvironments

Ist Teil von

• Cell reports (Cambridge), 2018-12, Vol.25 (13), p.3884-3893.e3

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• A major challenge in cancer research is the complexity of the tumor microenvironment, which includes the host immunological setting. Inspired by the emerging technology of organ-on-chip, we achieved 3D co-cultures in microfluidic devices (integrating four cell populations: cancer, immune, endothelial, and fibroblasts) to reconstitute ex vivo a human tumor ecosystem (HER2+ breast cancer). We visualized and quantified the complex dynamics of this tumor-on-chip, in the absence or in the presence of the drug trastuzumab (Herceptin), a targeted antibody therapy directed against the HER2 receptor. We uncovered the capacity of the drug trastuzumab to specifically promote long cancer-immune interactions (>50 min), recapitulating an anti-tumoral ADCC (antibody-dependent cell-mediated cytotoxicity) immune response. Cancer-associated fibroblasts (CAFs) antagonized the effects of trastuzumab. These observations constitute a proof of concept that tumors-on-chip are powerful platforms to study ex vivo immunocompetent tumor microenvironments, to characterize ecosystem-level drug responses, and to dissect the roles of stromal components. [Display omitted] •A complex HER2+ breast cancer ecosystem is reconstituted and quantitatively described•The effects of the drug trastuzumab (Herceptin) are directly visualized ex vivo•Trastuzumab promotes long cancer-immune interactions and an ADCC immune response•Trastuzumab and CAFs have antagonist immunomodulation effects Inspired by the emerging technology of tumor-on-chip, Nguyen et al. reconstituted ex vivo a human tumor microenvironment (HER2+ breast cancer), characterized the ecosystem-level responses to the drug trastuzumab (Herceptin), and dissected the roles of stromal components (immune cells and fibroblasts), demonstrating the power of immunocompetent tumors-on-chip for preclinical drug studies.