IMMU-05. MOLECULAR ANALYSES DEMONSTRATE AN IMMUNOSUPPRESSIVE PHENOTYPE IN THE CYST AND SOLID TUMOR COMPARTMENTS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA
Bibliographic record
Abstract
BACKGROUND: Adamantinomatous Craniopharyngioma (ACP) is associated with considerable short and long-term morbidity. There are currently no well-established directed therapies. Recent studies demonstrated pro-inflammatory characteristics in both the solid and cyst compartments, but no data have examined whether immunosuppressive mechanisms are active in these tumors. METHODS: This study utilized a variety of platforms to examine immunosuppressive markers in cyst fluid and associated solid tumor components of ACP. Analyte levels in ACP were compared with other common pediatric brain tumors and normal tissue in order to identify immunosuppressive factors that were overexpressed in ACP. Cyst fluid and cells contained therein were analyzed using multiplex cytokine analysis and flow cytometry, respectively. A large transcriptomic database of ACP and other pediatric tumors and normal brain was queried for immunosuppressive gene expression. Immunohistochemistry was used to further validate gene expression data. RESULTS: ACP demonstrated highly elevated levels of IDO-1 (FC 9.43 versus all other tumor/tissue types, p=1.4x10-28), confirmed by IHC staining for IDO-1 in the epithelial tumor compartment. Elevated levels of IL-10 were demonstrated in cyst fluid and solid tumor compartments. Myeloid cells from the ACP cyst compartment demonstrated low levels of CD64 and HLA-DR expression, combined with high levels of CD163 expression. This pattern is most consistent with an immunosuppressive, pro-tumor milieu. Both CD4 and CD8(+) T-cells demonstrated positive staining for PD-1, most consistent with an exhausted phenotype. Consistent with this, PD-L1 mRNA was elevated in ACP tumor samples versus many other tumor types. CONCLUSIONS: Pediatric ACP is characterized by immunosuppressive factors in both the solid and cyst fluid compartments. This finding must be further considered within the context of the pro-inflammatory characteristics that have been previously described. It further raises the prospect of clinical translation through the application of available immune-directed therapies, in particular those that elicit therapeutic benefit through reversal of immunosuppression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".