TMIC-53. TRANSGLUTAMINASE 2 EXPRESSION IN GLIOBLASTOMA: EVIDENCE FOR A ROLE IN EFFEROCYTOSIS
Bibliographic record
Abstract
Abstract Glioblastoma is the most common type of brain cancer in adults. It is currently incurable and there is a clear need for more effective treatments. The heterogeneity of this cancer and its ability to promote both local and systemic immunosuppression are major obstacles to the development of effective therapies. Previous studies have explored the use of transglutaminase 2 (TGM2) inhibitors for glioblastoma therapy. These studies focussed on TGM2 that is expressed in a subset of glioblastoma cells. We show here that glioblastoma-associated macrophages are a major source of TGM2 in glioblastoma tumours. Analysis of bulk and single cell RNAseq data showed that TGM2 mRNA was expressed at high levels in glioblastoma-associated macrophages. Immunohistochemical and immunofluorescence analysis of TGM2 expression was performed in a mouse xenograft model in which human mesenchymal subtype glioblastoma cells were grown intracerebrally in nude mice. In these xenograft tumours, glioblastoma cells were negative for TGM2 expression, while infiltrating macrophages were strongly positive. The most intense staining for TGM2 was observed in macrophages in the vicinity of necrotic regions. Apoptotic cells were frequently present within the necrotic regions and highly TGM2-positive macrophages were observed to be phagocytosing these. The same patterns of TGM2 expression were also observed in samples from glioblastoma patients. Consistent with a role in phagocytosis, TGM2 co-localized with the endosomal protein CD68 in glioblastoma-associated macrophages. The phagocytosis of apoptotic cells by macrophages, known as efferocytosis, is tolerogenic, both because it clears potentially antigenic material and because it induces an immunosuppressive phenotype in macrophages. As TGM2 has a previously established role in efferocytosis and autoimmunity suppression, our findings suggest that TGM2 has a role in maintaining the glioblastoma immunosuppressive environment and that its inhibition might enhance immunotherapy for this cancer.
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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 | 0.000 |
| 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".