Ex vivo quantification of anti-tumor T-cell activity upon anti-PD-1 treatment in patient-derived lung tumor-on-chip
veith, i.; mencattini, a.; nurmik, m.; damei, i.; lansche, c.; brosseau, s.; gropplero, g.; corgnac, s.; filippi, j.; pote, n.; mordant, p.; tosello, j.; sedlik, c.; piaggio, e.; girard, n.; camonis, j.; shirvani, h.; mami-chouaib, f.; mechta-grigoriou, f.; descroix, s.; martinelli, e.; zalcman, g.; PARRINI, M. C.
Show abstract
There is a compelling need for new approaches to predict efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate immune and stromal characteristics of a simplified tumor ecosystem. Here, we present the development and validation of lung-tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune check-point inhibitors on T-cell-mediated cancer cell death, by exploiting the power of live imaging and advanced image analysis algorithms. These tumor-on-chips were generated with patient-derived autologous primary cells isolated from fresh lung cancer samples, opening the path for applications in personalized medicine. Moreover, cancer-associated fibroblasts were shown to impair the response to anti-PD-1, indicating that tumor-on-chips are capable of recapitulating stroma-dependent mechanisms of immunotherapy resistance. This interdisciplinary combination of microfluidic devices, clinically-relevant cell models, and advanced computational methods, can innovatively improve both the fundamental understanding and clinical efficacy of immuno-oncology drugs.
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