Malignant T cells activate endothelial cells via IL-17 F
Bibliographic record
Abstract
Cutaneous T-cell lymphoma (CTCL) defines a group of lymphoproliferative disorders that primarily affects the skin. Mycosis fungoides (MF) is the most common clinical variant of CTCL comprising almost 50% of all patients diagnosed with primary T-cell lymphoma. 1 The etiology and pathogenesis of the disease remain poorly understood. Recent data suggest that environmental factors such as bacteria rather than heredity play an important role in the pathogenesis and disease progression. 2 3 4 Although angiogenesis generally plays a key role in tumor growth and metastasis and is considered one of the hallmarks of cancer, 5 little is known about angiogenesis in CTCL. However, recent data demonstrated that micro-vessel formation and the density of micro-vessels in CTCL skin lesions correlate with disease progression suggesting that angiogenesis plays a role in the pathogenesis. 6 Notably, malignant inflammation defined as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells plays a key role in disease progression (reviewed in ref. 7 ). Accordingly, we hypothesized that malignant T cells also orchestra angiogenesis in affected skin. In support, malignant T cells spontaneously produce angiogenic factors such as VEGF-A, VEGF-C and lymphotoxin-alpha 8 , 9 , 10 , 11 and induce increased vascularization and production of angiogenic factors in vivo . 12 Recent observations indicate that IL-17 family cytokines stimulate and modulate oncogenic angiogenesis. 13 Interestingly, due to abnormal activation of the JAK3/STAT3 signaling pathway, malignant T cells spontaneously express IL-17F and a fraction of MF patients display increased levels of IL-17A and/or IL-17F in lesional skin at levels comparable to those found in skin lesions from patients with psoriasis, 14 a disease which is also associated with increased angiogenesis. 15 Since malignant MF T cells constitutively express IL-17F and the expression in lesional skin is associated with progressive disease, 14 we hypothesized that malignant T cells partly promote angiogenesis through the expression of IL-17F in MF patients. Accordingly, we plated endothelial cells (HUVEC) on growth factor depleted matrigel in vitro with or without culture supernatant from malignant T cell lines (MyLa2059 and PB2B cells both of which spontaneously produce IL-17F 14 ) to assay for IL-17F mediated induction of endothelial sprouting and tube formation as described elsewhere. 11
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.005 | 0.006 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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".