TMIC-04. GLIOBLASTOMA-ASSOCIATED MYELOID CELLS DISPLAY NONPOLARIZED M0 MACROPHAGE PHENOTYPE
Bibliographic record
Abstract
The glioblastoma (GBM) microenvironment is commonly infiltrated with innate immune cells including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Presumably these cells assume a tumor-supportive alternatively activated M2 phenotype, but no comprehensive phenotypic and/or genotypic studies have been conducted yet. Flow cytometry analysis was utilized to determine the expression of M1 and M2 markers in the GBM-associated myeloid cells (GAMs). Whole-genome microarray analysis was performed using RNA isolated from GAMs and matched GBM-patient and healthy-donor blood myeloid cells. Nanostring Technology was used to profile immune system- and cancer-related genes in GAMs, matched GBM-patient blood myeloid cells, healthy-donor blood myeloid cells, normal human microglia, and nonpolarized M0 and M1-, M2a-, M2c-polarized macrophages. Gene Set Enrichment Analysis (GSEA) was used to identify hallmarks of biological states or processes in immune cells derived from GBM-patient blood and tissue compared to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs compared to macrophages. In contrast, microglia were the most common CD11b+cells isolated from nonmalignant surgical brain samples, with macrophages constituting the remaining contributor to the brain parenchyma. Classical GBMs had significantly higher number of MDSCs than macrophages, while the mesenchymal subtype had more microglia than MDSCs and macrophages. The number of GAMs positively corresponded with the overall tumor size (precisely with edema) but not with overall patient survival. Flow cytometry studies and gene expression profile analysis revealed that GAMs express both anti-tumor M1 and tumor-supportive M2 markers. GSEA identified biological processes in these cells relative to matched blood cells, including signaling by KRAS, TGF-β, and TNF-α, epithelial-mesenchymal transition, angiogenesis, and hypoxia. Unsupervised analysis of gene expression profiles showed that GAMs aligned closely with nonpolarized M0 macrophages. New immunotherapeutic strategies for GBM are needed to redirect nonpolarized M0 GAMs towards the M1 phenotype.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".