The role of IL-17/IL-6 axis in the development of chronic lymphocytic leukemia.
Bibliographic record
Abstract
e22119 Background: The tumor microenvironment (TME) is critical to the survival of tumor B cells in chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs) and the cytokines they produced are important components of TME. Methods: 49 Patients with various stages of CLL were included. BMMSCs were co-cultured with human CLL cells with or without the presence of IL-17. Peripheral blood mononuclear cells from CLL patients were injected into NSG mice and IL-6/IL-17 were delivered daily. Student t test and Pearson product-moment correlation were used in statistical analysis. Results: CLL cells survived better when co-cultured with BMMSCs. ELISA array revealed a high concentration of IL-6 in co-culture system. Inhibition of IL-6 by Actemra decreased CLL cell survival in the co-culture. IL-6 production can be induced by IL-17 in both BMMSCs and CLL cells. In a xenograft animal model, BMMSCs and its culture supernatant promoted the engraftment of CLL cells via inducing IL-6. Human recombinant IL-17 administration also increased CLL engraftment through inducing IL-6. The plasma of CLL patients had elevated levels of IL-6 (16.3 ± 8.1 vs. 2.6 ± 2.1 pg/mL, p < 0.001) and IL-17 (9.2 ± 8.0 vs. 1.4 ± 1.1 pg/mL, p < 0.001), compared to healthy controls. There was a linear correlation between the levels of IL-6 and IL-17 in CLL patients (p < 0.0001), but not in the healthy controls. The patients who received Fludarabine based chemotherapy (n = 18) had higher concentration of IL-6 (21.77 ± 12.25 vs. 10.33 ± 11.51 pg/mL, p < 0.001) and IL-17 (12.78 ± 8.20 vs. 4.42 ± 5.59 pg/mL, p < 0.001) compared to those untreated (n = 13). Patients with low levels IgA or IgM (n = 14) had elevated IL-6 concentration in their plasma compared to the controls (n = 33) (22.51 ± 13.00 vs. 10.20 ± 9.10 pg/mL, p = 0.001). IL-6 and IL-17 levels were not associated with tumor cell load, CD38 expression or β2-microglobulin in our cohort of patients. Conclusions: Our study suggests an important role of IL-6 in survival of CLL cells. High levels of IL-17 in CLL patients may be responsible for the elevation of IL-6. CLL patients with higher IL-6 or IL-17 levels tend to have more aggressive diseases. IL-17/IL-6 axis could be a therapeutic target in CLL treatment.
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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 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".