Atypical B Cells Promote Cancer Progression and Poor Response to Bacillus Calmette-Guérin in Non–Muscle Invasive Bladder Cancer
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Poor response to Bacillus Calmette-Guérin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle invasive bladder cancer (NMIBC). Multiple factors are associated with poor outcomes, including biological aging and female sex. More recently, it has emerged that a B-cell-infiltrated pretreatment immune microenvironment of NMIBC tumors can influence the response to intravesically administered BCG. The mechanisms underlying the roles of B cells in NMIBC are poorly understood. Here, we show that B-cell-dominant tertiary lymphoid structures (TLSs), a hallmark feature of the chronic mucosal immune response, are abundant and located close to the epithelial compartment in pretreatment tumors from BCG non-responders. Digital spatial proteomic profiling of whole tumor sections from male and female patients with NMIBC who underwent treatment with intravesical BCG, revealed higher expression of immune exhaustion-associated proteins within the tumor-adjacent TLSs in both responders and non-responders. Chronic local inflammation, induced by the N-butyl-N-(4-hydroxybutyl) nitrosamine carcinogen, led to TLS formation with recruitment and differentiation of the immunosuppressive atypical B-cell (ABC) subset within the bladder microenvironment, predominantly in aging female mice compared to their male counterparts. Depletion of ABCs simultaneous to BCG treatment delayed cancer progression in female mice. Our findings provide evidence indicating a role for ABCs in BCG response and will inform future development of therapies targeting the B-cell-exhaustion axis.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 it