Polyfunctional <scp>CD</scp> 8 <sup>+</sup> <scp>CD</scp> 226 <sup>+</sup> <scp>RUNX</scp> 2 <sup>hi</sup> effector T cells are diminished in advanced stages of chronic lymphocytic leukemia
Bibliographic record
Abstract
CD8 + T cells, a subset of T cells identified by the surface glycoprotein CD8, particularly those expressing the co‐stimulatory molecule CD226, play a crucial role in the immune response to malignancies. However, their role in chronic lymphocytic leukemia (CLL), an immunosuppressive disease, has not yet been explored. We studied 64 CLL patients and 25 age‐ and sex‐matched healthy controls (HCs). We analyzed the proportion of CD226‐expressing cells among different CD8 + T cell subsets (including naïve, central memory, effector memory, and effectors) in CLL patients, stratified by Rai stage and immunoglobulin heavy‐chain variable region gene (IgHV) mutation status. Additionally, we compared the effector functions of CD8 + CD226 + cells and their CD226 − counterparts. We also quantified cytokine and chemokine levels in the plasma of CLL and HCs. Furthermore, we reanalyzed the publicly available bulk RNA‐seq on CD226 + and CD226 − CD8 + T cells. Finally, we evaluated the impact of elevated cytokines/chemokines on CD226 expression. Our results showed that CD226 ‐expressing cells were significantly decreased within the effector memory and effector CD8 + T cell subsets in CLL patients with advanced Rai stages and unmutated IgHV, a marker of poor prognosis. These cells displayed robust effector functions, including cytokine production, cytolytic activity, degranulation, proliferation, and migration capacity. In contrast, CD8 + CD226 − T cells displayed an exhausted phenotype with reduced Runt‐related transcription factor 2 ( RUNX2 ) expression. Elevated levels of interleukin‐6 (IL‐6) and macrophage inflammatory protein‐1 beta (MIP‐1β) were inversely correlated with the frequency of CD8 + CD226 + T cells and may contribute to the downregulation of CD226, possibly leading to T cell dysfunction in CLL. Our findings highlight the critical role of CD8 + CD226 + RUNX2 hi T cells in CLL and suggest that their reduction is associated with disease progression and poor clinical outcomes. This study also underscores the potential of targeting IL‐6 and MIP‐1β to preserve polyfunctional CD8 + CD226 + T cells as a promising immunotherapy strategy.
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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) | 0.004 | 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".