An Engineered Patient‐Derived Tumor Organoid Model That Can Be Disassembled to Study Cellular Responses in a Graded 3D Microenvironment
Bibliographic record
Abstract
Abstract Patient‐derived organoids (PDOs) are emerging as powerful models to capture the genetic heterogeneity of human tumors. However, the self‐assembling nature of PDOs limits their use in studies of the impact of microenvironmental heterogeneity on tumor cell function. Here, a paper‐based model, the Tissue Roll for Analysis of Cellular Environment and Response (TRACER) is adapted, using patterned polymer infiltration, to enable controlled assembly and disassembly of organoid structures to study the impact of both genetic and microenvironmental heterogeneity on tumor cell behavior. In the adapted platform (TRACER2), pancreatic cancer PDOs establish oxygen gradients across the tissue and in response exhibit graded cell viability, proliferation, hypoxia‐response gene transcription, and response to gemcitabine therapy. Further, PDOs retrieved from the hypoxic regions of the TRACER2 cultures show graded transcriptional changes in immunosuppression‐related genes and upon co‐culture, after TRACER2 disassembly, induce graded functional changes in Jurkat cells and macrophage cells. Therefore, TRACER2 offers a novel platform to dissect the effects of microenvironmental parameters on tumor cell function.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".