Tumour–Host Immunodynamics of Bacillus Calmette Guérin (BCG) Refractory Bladder Cancer
Bibliographic record
Abstract
Introduction: Bladder cancer (BC) is dichotomized into muscle–invasive (MIBC) and non–muscle invasive (NMIBC), depending on tumour invasion across the lamina propria. Most BC patients are initially diagnosed with NMIBC. Intravesical administration of Bacillus Calmette-Guérin (BCG) has been considered the gold standard for high–risk NMIBC following tumour surgical removal. While BCG is established as a clinically beneficial immunotherapy, around 50% of patients recur or progress into the more aggressive MIBC. We aim to better understand the molecular underpinnings of BCG–mediated immune response profiles among responders and non–responders. Methods: Peripheral blood mononuclear cells were isolated from two blood draws of 16 patients with intermediate– and high–risk NMIBC, the first preceding treatment and the second following the fifth BCG installation (n = 32 samples). Patients were classified based on remission (n = 8) and recurrence (n = 8) within one year. Single–cell RNA sequencing determined immune cell type transcriptomic changes. Differential expression and pathway enrichment analyses were conducted to identify immune signatures differentiating responders from non–responders and the first (Week 1) versus last (Week 6) week of BCG management. Results: Regarding the transcriptome, an elevated metabolic response to BCG was detected in monocyte populations within responders. Particularly, mechanistic target of rapamycin complex I (mTORC1) signalling was upregulated in Week 6 compared to Week 1 within responders. Conversely, non–responders experienced downregulation of mTORC1 post–BCG. At Week 1, non–responders displayed a pre–inflammatory state that may underlie treatment resistance, marked by an upregulation of inflammatory pathways, ex. interferon (IF)–γ and tumour necrosis factor (TNF)–α. Conclusion: In NMIBC, non–responders to BCG immunotherapy display a preceding immune dysfunction characterized by metabolic and inflammatory disturbances. Pre–treatment peripheral immune profiling may effectively predict therapeutic outcomes and further personalize treatments for patients with early–stage NMIBC.
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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 | 0.000 | 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) | 0.001 | 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".