The Clinical Relevance of Tertiary Lymphoid Structures in Assessing Treatment Response in Muscle-Invasive Bladder Cancer
Bibliographic record
Abstract
PURPOSE: Radical cystectomy (RC) is a standard of care for muscle-invasive bladder cancer (MIBC). Although radiation therapy (RT) offers bladder preservation with comparable survival, 20%-30% of patients require salvage RC. Neoadjuvant chemotherapy (NAC) is given to patients prior to RC, but with modest benefit and considerable toxicity. Among tumor immune microenvironment features, tertiary lymphoid structures (TLS) have emerged as prognostic and predictive biomarkers. Here, we investigate the association between TLS and response to RT and NAC in MIBC. METHODS AND MATERIALS: We evaluated TLS in pre-treatment transurethral resection of bladder tumor specimens from MIBC patients given RT or NAC. Multiplex immunohistochemistry defined TLS presence, density, and maturation, including germinal center and immune subset markers. Associations with treatment response and survival were analyzed separately for RT and NAC cohorts. RESULTS: TLS were detected in 83% of RT patients. Although the presence was not prognostic, higher density and maturation correlated with response and with improved overall and cancer-specific survival. Furthermore, TLS density correlated with B cells and regulatory T cells (Tregs) in responders and inversely with cytotoxic T cells in nonresponders. In the NAC cohort, TLS presence, density, or maturation were not associated with response or survival. CONCLUSIONS: These exploratory findings suggest that TLS density and maturation may be associated with improved RT outcomes in MIBC and warrant prospective validation as biomarkers.
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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 | 0.004 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".