Microdissected tumor cuboids: a microscale cancer model that retains a complex tumor microenvironment
Horowitz, L. F.; Rodriguez-Mias, R. A.; Zhu, S.; Gottshall, N. R.; Stepanov, I.; Stiles, C.; Yeung, M.; Nguyen, T. N.; Lockhart, E. J.; Yeung, R. S.; Villen, J.; Gujral, T. S.; Folch, A.
Show abstract
To bridge the gap between bench and bedside, there is a need for more faithful models of human cancers that can recapitulate key features of the human tumor microenvironment (TME) and simultaneously facilitate large-scale drug tests. Our recently developed microdissection method optimizes the yield of large numbers of cuboidal microtissues ("cuboids", [~](400 {micro}m)3) from a 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 expression and drug responses, including to immunotherapy. Overall, our results suggest that cuboids could provide essential therapeutic information for personalized oncology applications and could help the development of TME-dependent therapeutics and cancer disease models, including for clinical trials.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Multiplexed drug testing of tumor slices using a microfluidic platform 97%
- A patient-derived ovarian cancer organoid platform to study susceptibility to natural killer cells 94%
- Single-Cell Spatial Proteomics Analyses of Head and Neck Squamous Cell Carcinoma Reveal Tumor Heterogeneity and Immune Architectures Associated with Clinical Outcome 94%
Similar papers in this journal
- Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications in a common base culture media system 96%
- Intracellular Optical Doppler Phenotypes of Chemosensitivity in Human Epithelial Ovarian Cancer 95%
- Proteogenomic Characterization of Triple-Negative Apocrine Carcinoma Reveals Molecular Features of Progression and Chemotherapy Response 94%
Similar papers in this journal
- Functional single-cell profiling identifies that exosomes are associated with increased immune cell infiltration in non-metastatic breast cancer 96%
- Propagated circulating tumor cells uncovers the rople of NFκB and COP1 in metastasis 95%
- In vivo optical metabolic imaging of long-chain fatty acid uptake in orthotopic models of triple negative breast cancer 94%
Similar papers in this journal
- Low-Cost Robotic Manipulation of Live Microtissues for Cancer Drug Testing 97%
- Dual-Mode Microfluidic Immunostaining (Dumi) Device for Diagnostic Biomarkers Detection and Tumor Microenvironment Evaluation 94%
- Dormancy-inducing 3D-engineered matrix uncovers mechanosensitive and drug protective FHL2-p21 signaling axis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.