Combining Antiandrogens with Immunotherapy for Bladder Cancer Treatment
Bibliographic record
Abstract
Background: Men are three to four times more likely to be diagnosed with bladder cancer (BCa) than women, who often have more aggressive tumors. Intravesical bacillus Calmette-Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC) is one of the first immunotherapies, with use of immune checkpoint inhibitors for BCa immunotherapy expanding. Sex hormones, and notably androgens, might impact the outcome of these therapies. Objective: To understand immunological sex differences in BCa and investigate androgen receptor (AR) inhibition as a novel strategy to improve the response to BCa immunotherapy. Design setting and participants: studies used the subcutaneous MBT-2 BCa model in male and female C3H mice. The AR antagonist enzalutamide was given alone or in combination with anti-programmed cell death protein-1 (anti-PD-1) or intratumoral BCG + poly(I:C) treatments. Outcome measurements and statistical analysis: . Flow cytometry and RNA sequencing characterized the immune cells present in murine and human tumors. Descriptive comparisons were performed for MBT-2 tumors between sexes and with human NMIBC tumors. Results and limitations: The MBT-2 model shows multiple similarities to the immune composition of human NMIBC tumors and recapitulates previously observed human tumor immune cell sex differences. Enzalutamide in combination with either anti-PD-1 or BCG + poly(I:C) treatment in male mice synergized to improve response rates. Notably, the proportion of complete responses in male mice treated with the combination treatment resembles that observed in female mice with either immunotherapy alone. Limitations include the sample size for murine experiments. Conclusions: Our results suggest that combining AR antagonism with immunotherapy in male BCa patients may potentiate the antitumor immune response and increase response rates. The MBT-2 model appears relevant to investigate immunological BCa sex differences. Patient summary: Our studies suggest that combining antiandrogen treatments with BCa immunotherapy may improve response rates in men. We also demonstrate the utility of the MBT-2 mouse model to study sex differences in BCa.
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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) | 0.002 | 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 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".