STEM-04. PD-1 INDEPENDENT OF PD-L1 LIGATION PROMOTES GLIOBLASTOMA GROWTH THROUGH THE NFkB PATHWAY
Bibliographic record
Abstract
Abstract Brain tumor-initiating cells (BTICs) drive glioblastoma growth through not fully understood mechanisms. Here, we found that a proportion of human and murine BTICs expressed programmed cell death protein (PD-1). Gain- or loss-of-function studies revealed that tumor-intrinsic PD-1 promoted proliferation, and self-renewal of BTICs. Mechanistically, site-directed mutagenesis, RNA sequencing and pharmacological inhibitors implicated SHP-2-mediated activation of NFkB downstream of PD-1 in BTICs. Notably, the tumor-intrinsic promoting effects of PD-1 did not require PD-L1 ligation; thus, the therapeutic blocking antibodies inhibiting PD-1/PD-L1 interaction which failed in glioblastoma trials could not overcome the growth advantage of PD-1 in BTICs. Finally, mice with intracranial Pdcd1 over- or underexpressing BTICs had shorter or longer survival, respectively, and this occurred in mice lacking T and B cells. These findings point to a critical role for PD-1 in BTICs and uncover a non-immune resistance mechanism of GBM patients to PD-1 or PD-L1 blocking therapies.
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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) | 0.000 | 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".