Inhibition of PAK2 in endothelial cells suppresses tumor angiogenesis and promotes immune sensitization through CXCL10
Bibliographic record
Abstract
Tumor angiogenesis is driven by pro-angiogenic factors and results in a disorganized tumor vasculature that limits effective perfusion and immune infiltration. The p21-activated kinase 2 (PAK2) regulates endothelial cell (EC) migration, an essential step in angiogenesis, yet its role in tumor angiogenesis remains ill-defined. Here, we show that endothelial-specific deletion of PAK2 in orthotopic tumor mouse models markedly reduces tumor size and angiogenesis. Additionally, loss of endothelial PAK2 normalizes the remaining tumor vasculature and promotes infiltration of dendritic and natural killer cells. Mechanistically, PAK2 regulates chemokine expression, notably CXCL10. PAK2 depletion enhances CXCL10 secretion from ECs, and CXCL10 expression is required for the inhibitory effects of PAK2 silencing on EC sprouting. Moreover, CXCL10 neutralization in mice reverses the vascular and immune changes induced by endothelial PAK2 deletion. Together, these findings identify endothelial PAK2 as a potential target to limit tumor angiogenesis and reprogram ECs to promote immune infiltration through CXCL10 signaling.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".