Targeting immune evasion mediated by LOX-1+ neutrophils in Hodgkin Lymphoma via nanobodies antagonistic for CD39 enzymatic activity
Bibliographic record
Abstract
Introduction Hodgkin Lymphoma is one of the most common malignancies in children and adolescent and a classic example of tumour-mediated immune evasion. Here, we interrogated the role of neutrophilic granulocytes in Hodgkin Lymphoma Methods We combined clinical data analysis, in vitro functional assays, flow cytometry, and transcriptomic profiling to investigate the systemic role and immunomodulatory potential of neutrophils in pediatric Hodgkin Lymphoma. Results We observed pronounced dysregulation at initial diagnosis, including elevated absolute neutrophil counts and significantly increased initial neutrophil to lymphocyte ratio in those with relapse. Further, we identified dysregulation of neutrophil-related cytokines in pediatric Hodgkin Lymphoma patients, implicating neutrophils in disease progression. In vitro exposure of healthy neutrophils to HL cell line supernatants induced morphological and phenotypic changes, including upregulation of LOX-1, a marker of immunosuppressive neutrophils. Functionally, these HL-primed neutrophils suppressed T-cell proliferation and cytokine secretion. Transcriptomic profiling confirmed a distinct program in HL-primed neutrophils, with upregulated genes related to ROS generation and innate immunity. Immunosuppression was partially reversed by ROS inhibition and substantially reversed by a biparatopic nanobody targeting CD39 enzymatic activity, identifying extracellular ATP degradation as a key suppressive mechanism. While neutrophils were scarce in tumour tissues, patient-derived serum induced similar immunosuppressive phenotypes in healthy neutrophils, confirming systemic modulatory effects. Conclusion These findings reveal that neutrophils are reprogrammed by HL to support immune evasion on a systemic level with CD39 as potential therapeutic target. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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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) | 0.001 | 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 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".