IMMU-19. QUANTITATION AND CHARACTERIZATION OF GLIOBLASTOMA-ASSOCIATED MICROGLIA AND MACROPHAGES REVEALS HIGHLY VARIABLE INFLAMMATORY PROFILES AND AN INVERSE RELATIONSHIP TO PERITUMORAL EDEMA VOLUME
Bibliographic record
Abstract
Innate immune cells in the CNS, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are co-opted by GBM to adopt anti-inflammatory, immunosuppressive phenotypes and aid neoplastic progression. The bulk of immunotherapy research in GBM has been directed at T cells, which are part of the adaptive immune system, but make up a much smaller part of the inflammatory infiltrate. An effective immunotherapy against GBM has still not been found, in part because of a lack in understanding of GBM-associated MMs and the way they affect the immune microenvironment in which T cell therapies are expected to work. Our studies on human GBM tissue have uncovered there is surprisingly marked variation in the amount of MM infiltration between tumors, and this has bearing on clincopathologic parameters. Using automated quantitation methods, immunohistofluorescence, and validation with flow cytometry, we found that MM infiltration can range from almost non-existent, to comprising approximately 70% of GBM cells. With canonical markers and conditioned media, we determined that a mixture of pro-inflammatory and anti-inflammatory MMs were found in each tumor. Despite having a similar level of infiltration, GBM-associated MMs could still have drastically different gross inflammatory profiles. Age at diagnosis, time to progression, overall survival, comorbidities, and tumor volume were not associated with extent of MM infiltration. However, volumetric MRI analysis revealed heavier MM infiltration correlated with decreased peritumoral edema, contrary to previous reports. Taken together, we have found the inflammatory nature of the immune infiltrate can be drastically different between GBMs, and can have clinically significant effects on parameters such as peritumoral edema. These findings also demonstrate the importance of tailoring immunotherapies to individual patients given the considerable variability in magnitude and immunosuppression of the innate immune cells in the GBM microenvironment.
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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 | 0.001 | 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 | 0.000 | 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".