T‐CELL SUBSET COMPOSITION AND FUNCTIONALITY IN PATIENTS WITH WALDENSTRÖM’S MACROGLOBULINEMIA
Notice bibliographique
Résumé
Background: Waldenström's macroglobulinemia (WM) is an incurable low-grade B-cell Non-Hodgkin lymphoma. WM resembles chronic lymphocytic leukemia (CLL) with regard to biologic and clinical characteristics. In CLL, extensive abnormalities in T-cell subset distribution and function have been described. These alterations may contribute to disappointing responses to T-cell directed immunotherapies. Novel autologous T-cell directed immunotherapy may improve the outlook for WM patients. However, studies evaluating T-cell functionality in WM are lacking. Methods: We systematically evaluated peripheral blood (PB) T-cell subset composition and function in WM patients. PB samples were collected from treatment-naive, relapsed and symptomatic WM patients, HCs and treatment-naïve CLL patients. Lymphocyte phenotyping was performed and differences in functionality were assessed by determining the potential of T-cells to degranulate and produce cytokines. Cytotoxic potential was assessed via engagement of blinatumomab (CD3 x CD19 bi-specific T-cell engager), that re-directs T-cells via CD3 to kill CD19+ tumor cells. Correlations between T-cell subset numbers, cytokine production, cytotoxic capacity and markers of disease activity were performed for treatment-naïve and pretreated WM separately. Results: This study included 16 treatment-naïve WM patients, 10 pretreated symptomatic WM patients, 21 age-matched HCs and 17 treatment-naïve CLL patients. In WM patients, following cell types had counts similar to HCs: T-cells (relative), CD4+ T-cells (relative), absolute CD4+ and CD8+ T-cells, Tfh cells, Treg cells, and Vδ1/ Vδ2 T-cells (relative). This is in contrast to CLL, in which T-cell numbers (relative) were decreased, absolute CD4+ and CD8+ T-cells were increased compared to HCs, Tfh, Treg, and Vδ1 T-cell numbers were increased as expected. CD4+/CD8+ T-cell differentiation was normal in WM as opposed to CLL in which a known skewing towards terminal differentiation in CD8+ T-cells was observed. No difference in Vδ2 T-cell count was observed between all groups (Figure 1). No significant differences were found in cytokine production and degranulation between CD4+ and CD8+ T-cells from WM patients in comparison with HCs, in contrast to CLL in which decreased amounts of TNF-α and increased expression of CD107a were found. Cytotoxic potential of WM-derived T-cells was intact and similar to HCs, while CLL-derived T-cells have impaired cytotoxic response to blinatumomab. Conclusion: These data represent the first systematic evaluation of the T-cell compartment in WM. The qualitative and quantitative changes in the immune system seen in CLL are not found in WM; T-cell numbers, distribution and functionality seem mostly preserved even in pretreated patients. These findings are encouraging for application of T-cell directed immunotherapy in WM, especially for relapsed/refractory WM. Keywords: Immunotherapy, Indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».