INTEGRATED EFFICACY AND SAFETY ANALYSIS OF LETETRESGENE AUTOLEUCEL, A T-CELL RECEPTOR T-CELL THERAPY, ACROSS CLINICAL TRIALS OF PATIENTS WITH SYNOVIAL SARCOMA AND MYXOID/ROUND CELL LIPOSARCOMA
Bibliographic record
Abstract
unified cohort of 134 patients was formed using tissue microarrays from two sarcoma centers: 109 cases from MD Anderson Cancer Center and 25 from Fred Hutchinson Cancer Center (FHCC).Two mIHC panels were used: CD4, CD68/CD163, CD8, FoxP3, PD-1, PD-L1 (with post-mIHC ERG DAB) and CD68, CD20, CD3, CD163, CD206, CD34.Transcriptomic analysis was performed using the NanoString IO 360 panel on 25 angiosarcoma samples from FHCC with 9 hemangiomas as controls. Results:We observed significant differences in immune cell infiltration between cutaneous and non-cutaneous angiosarcomas, with higher levels of CD20+ B-cells (p=0.015),CD3+ T-cells (p=0.007),CD8+ T-cells (p< 0.001), FOXP3+ regulatory Tcells (p< 0.001), PD1+ cells (p=0.004) and CD4+ T-cells (p=0.015) in cutaneous tumors.Survival analysis demonstrated that higher CD20+ B-cell infiltration was significantly associated with improved overall survival (p=0.014).Gene expression analysis revealed higher MAPK pathway-related transcripts including MAP4K2 and MAPKAPK2 in angiosarcomas.Angiosarcomas also had higher complement levels (C5/C6), and lower expression of interleukin 1 receptor antagonist (IL1RN).When comparing angiosarcoma subtypes, scalp/face tumors showed distinctive immune profiles with lower complement expression and higher expression of inflammatory markers S100A8, S100A9, NOD2, and IL1B; paired with higher CD3+ and CD4+ cell infiltration on mIHC compared to other sites. Conclusion:These findings provide insights into the immunological landscape of angiosarcomas across different anatomical locations.The significantly higher immune infiltration in cutaneous versus non-cutaneous angiosarcomas suggests distinct immunological mechanisms, consistent with higher immunotherapy responsiveness in cutaneous angiosarcomas.Our results suggest that immune cell infiltration, particularly CD20+ B-cells, may serve as prognostic biomarkers in this rare disease.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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".