Human Glioma Immunobiology in Vitro: Implications for Immunogene Therapy
Bibliographic record
Abstract
OBJECTIVE: Human gliomas are known to be immunosuppressive. Recent reports have suggested novel strategies to overcome this immunosuppression, including immunogene therapy. We examined expression of 10 immunologically important molecules by human gliomas in vitro, and we discuss the implications for immunogene therapy. METHODS: Early passage human glioma cultures and established human glioma cell lines were analyzed by flow cytometry for expression of Class I and II major histocompatibility complex (MHC), B7-2 (CD86), and Fas (CD95). Culture supernatants were assayed by enzyme-linked immunosorbent assay for interleukin (IL)-6, IL-10, IL-12, transforming growth factor beta2, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor levels. RESULTS: All cultures (16 of 16 samples) expressed Class I MHC and Fas, but few expressed Class II MHC (1 of 16 samples) or B7-2 (0 of 16 samples). Nearly all expressed high levels of IL-6 (19 of 21 samples; mean, 36.5 +/- 10.8 ng/10(6) cells/d) and prostaglandin E2 (21 of 21 samples; mean, 15.6 +/- 4.5 ng/10(6) cells/d) levels, and many expressed transforming growth factor beta2 (13 of 21 samples; mean, 8.6 +/- 3.7 ng/10(6) cells/d). Although several cultures (6 of 14 samples) expressed granulocyte-macrophage colony-stimulating factor, expression levels were very low (mean, 0.2 +/- 0.1 ng/10(6) cells/d). Few cultures (4 of 21 samples) expressed measurable IL-10, and none (0 of 22 samples) expressed IL-12. CONCLUSION: Class I MHC and Fas expression suggests that human glioma cells may be susceptible to Class I MHC-dependent cytotoxic T cell recognition and Fas-mediated killing. Unfortunately, transforming growth factor beta2 and prostaglandin E2 probably impair T cell activation, and IL-6 may shift immunity to less effective humoral (T helper 2) responses. Proinflammatory gene expression (B7-2, granulocyte-macrophage colony-stimulating factor, and/or IL-12) is lacking. Together, these results suggest that modifying glioma cells via proinflammatory gene transfer or immunoinhibitory gene suppression might stimulate immune responses that are effective against unmodified tumors.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".