Tumor-driven stromal reprogramming in the pre-metastatic lymph node
Bibliographic record
Abstract
Background: Metastatic dissemination is critically reliant on the formation of a receptive niche, a process which is thought to rely on signals derived from the primary tumor. Lymph nodes are continuously exposed to such signals through the flow of afferent lymph, allowing the potential reprograming of lymphoid tissue stroma in support of metastases or immunosuppression. The objective of this study was therefore to better characterize tumor-driven transcriptomic changes occurring to specific stromal populations within the tumor-draining lymph node. Methods: We utilize single cell RNA sequencing of dissociated LN tissue extracted from tumor-bearing and naïve mice to profile the reprograming of tissue stroma within the pre-metastatic lymph node. Results: Resulting data provides transcriptomic evidence of tumor-induced imprinting on marginal reticular cells (MRCs) and floor lymphatic endothelial cells (fLECs) populating the subcapsular sinus. These alterations appear to be unique to the tumor-draining LN and are not observed during inflammatory antigenic challenge. Notably, MRCs exhibit characteristics reminiscent of early desmoplastic CAF differentiation, fLECs engage distinct chemoattractant pathways thought to facilitate recruitment of circulating cancer cells, and both stromal populations exhibit signs of metabolic reprograming and immune-modulating potential. Conclusions: Cumulatively, these findings build upon existing literature describing pre-metastatic niche formation and offer several promising avenues for future exploration.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".