Identification of immune evasion strategies of pediatric pre-B acute lymphoblastic leukemia after bone marrow transplantation
Bibliographic record
Abstract
8555 Background: Bone marrow transplantation (BMT) is the only curative option for refractory/relapsed pediatric acute lymphoblastic leukemia (ALL). However, post-BMT relapse remains an important cause of transplantation failure. Immune mechanisms play a critical role in the anti-leukemic efficacy of BMT, suggesting that mechanisms allowing leukemic blasts to evade immune responses are important in leukemia relapse. An improved understanding of the processes underlying post-BMT ALL relapse is required. Methods: In this study several methods were utilised to assess and compare the allogeneic and autologous T cell responses induced by pediatric pre-B ALL cells which had been obtained at various time points from a pediatric patient with pre-B ALL who relapsed following allogeneic BMT. All patient samples were also extensively phenotyped in order to determine the degree of co-stimulatory molecule expression on the leukemic blasts. Results: We observed a dramatic loss of T cell stimulatory capacity by later relapse samples. Also, the autologous anti-leukemic T cell response demonstrated a Th2 shift compared to the Th1 allogeneic response. These immune stimulatory changes induced by ALL cells at relapse were associated with changes in expression of MHC and costimulatory molecules. HLA-ABC expression was increased on all relapse samples. HLA-DR expression was substantially reduced in those relapse samples obtained following immunosuppression cessation. Expression of the costimulatory molecule CD137L was decreased on post-BMT relapse samples whereas B7-H1 expression was increased. Conclusions: These results reveal mechanisms involved in pre-B ALL relapse, and suggest strategies to prevent evasion of the graft-versus-leukemia effect by ALL cells. No significant financial relationships to disclose.
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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".