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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 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 tête enseignante, 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 ».