TMIC-10PLEIOTROPY OF TUMOR-ASSOCIATED MYELOID CELLS WITHIN HUMAN GLIOBLASTOMA
Bibliographic record
Abstract
INTRODUCTION: GBM is highly infiltrated by diverse immune cells including microglia, monocyte-derived macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms through which glioblastoma-associated myeloid cells (GAMs) undergo a metamorphosis into tumor supportive cells, characterizing the heterogeneity of immune cell phenotypes within GBM subtypes and discovering new targets can help to design new efficient immunotherapies against GBM. METHODS: GAMs were isolated from GBMs by immunomagnetic separation (n = 17) and microglia were identified as CD11b+CD45low, MDSCs as CD11b+CD33+CD45med, and macrophages as CD11b+CD45high. Whole genome microarray analysis (30,275 human genes) was performed using RNA isolated from the GAMs and matched blood monocytes. Comparisons were also made between GAMs and healthy donor monocytes (n = 11), normal adult human brain microglia (n = 9), and normal human CD14+ monocytes polarized into the M0, M1, M2a, and M2c phenotype (n = 5) using flow cytometry, and gene/microRNA expression profiling. RESULTS: GBM patients had elevated monocytes relative to normal donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GBM-infiltrating immune cells compared to macrophages. GAM profiling revealed a continuum between anti-tumor pro-inflammatory M1- (MHC II, CD80, CD86, p-STAT1, TNF-α) and tumor-supportive M2-like (CD163, CD206, p-STAT3, TGF-β1, IL-10) myeloid cells, with immune functional assays indicating greater alignment with M2. Flow cytometry studies and gene expression analysis demonstrated, that M1-and M2-polarized macrophages expressed a unique mixed M1/M2 phenotype. GAMs and GBM patient blood monocytes showed distinct immunological functions with the former aligned closer to an M2 phenotype that seemed to play a crucial role in GBM invasiveness and progression. CONCLUSIONS: Within GBM, microglia and MDSCs constitute the majority of tumor-infiltrating myeloid cells that express genes within the continuum of M1/M2 with alignment favoring M2 indicating GAMs have pleiotropic immunological functions.
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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".