Microdissected tumor cuboids: a microscale cancer model for large-scale testing that retains a complex tumor microenvironment.

Current cancer disease models fail to faithfully recapitulate key features of the human tumor microenvironment (TME), such as immune and vascular cells, while simultaneously enabling high-throughput drug tests. We have recently developed a precision slicing method that optimizes the yield of large numbers of cuboidal microtissues ("cuboids", ∼(400 µm) 3 ) from a single tumor biopsy. Here we demonstrate that cuboids from syngeneic mouse tumor models and human tumors retain a complex TME, making them amenable for drug and immunotherapy evaluation. We characterize relevant TME parameters, such as cellular architecture, cytokine secretion, proteomics profiles, and response to drug panels in multi-well arrays. Despite the cutting procedure and the time spent in culture (up to 7 days), the cuboids display strong cytokine and drug responses, including to immunotherapy. Overall, our results suggest that cuboids could provide invaluable therapeutic information for personalized oncology applications, and could help the development of TME-dependent therapeutics and cancer disease models, including for clinical trials.