T‐CELL SUBSET COMPOSITION AND FUNCTIONALITY IN PATIENTS WITH WALDENSTRÖM’S MACROGLOBULINEMIA
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".