MNGI-12. EXPRESSION OF PROGRAMMED CELL DEATH LIGAND-1 (PD-L1) IN MENINGIOMA: CLINICAL UTILITY FOR PREDICTION OF TUMOR RECURRENCE AND ASSOCIATION WITH HYPOXIC RESPONSE AND NFKB2 ACTIVATION
Bibliographic record
Abstract
Tumor recurrence is one of the most important clinical challenges in the management of meningioma patients. Prognostic significance of PD-L1 as a driver for immunosuppressive response and predictor for tumor growth has been demonstrated in several malignancies. We studied the prognostic role of PD-L1 expression for tumor recurrence in meningioma and explored underlying activation mechanisms. We analyzed a total of 93 meningioma cases diagnosed between 1998 and 2016 at University Health Network: F/M ratio 58/35; WHO grades I (43), II (42), III (9) with 47% recurrence rate and median follow up 6.97 years. Immunohistochemical (IHC) analysis on tumor sections showed PD-L1 expression in 33 (35%) cases with distinctive patchy distribution. Univariate and multivariate analyses confirmed that PD-L1 expression is an independent prognostic marker for recurrence free survival(RFS) in meningioma patients after adjusting for extent of resection, WHO grade, and maximum tumor diameter (p<0.0001). Additionally, we performed Gen Set Enriched Analysis (GSEA) on RNA seq data from 88 meningiomas using HUVEC hypoxia Dataset GSE89831 as reference to calculate hypoxia levels. Our results indicated that hypoxic meningiomas have significantly elevated PD-L1 expression. Furthermore, we investigated expression of PD-L1 in 3 different meningioma cell lines under normoxic and hypoxic conditions by real-time PCR. We found that in addition to the expected HIF1a target genes, PD-L1 mRNA level increased when exposed to hypoxic condition. Analysis of RNAseq data from two GEO meningioma studies demonstrated prominent NFKB2 activation associated with PD-L1 mRNA expression. IHC analysis confirmed expression of NFKB2 protein in 26 (30%) cases, which correlated with PD-L1 expression. Our data strongly suggest the clinical utility of PD-L1 expression for prediction of tumor recurrence and a potential link between hypoxia and anti-cancer immunity in meningioma patients. These results also provide a rationale for a potential therapeutic role for PD-L1 inhibitors in clinically aggressive meningioma.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".