Combining Antiandrogens with Immunotherapy for Bladder Cancer Treatment.
Antiandrogens
Bladder cancer
Immunotherapy
MBT-2 model
Journal
European urology open science
ISSN: 2666-1683
Titre abrégé: Eur Urol Open Sci
Pays: Netherlands
ID NLM: 101771568
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
accepted:
17
06
2022
entrez:
17
10
2022
pubmed:
18
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
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. To understand immunological sex differences in BCa and investigate androgen receptor (AR) inhibition as a novel strategy to improve the response to BCa immunotherapy. Human NMIBC tumors were freshly collected following transurethral resection. Tumor growth and survival were evaluated 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. 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. 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.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
Human NMIBC tumors were freshly collected following transurethral resection.
Outcome measurements and statistical analysis
UNASSIGNED
Tumor growth and survival were evaluated
Results and limitations
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
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.
Identifiants
pubmed: 36246841
doi: 10.1016/j.euros.2022.06.007
pii: S2666-1683(22)00723-6
pmc: PMC9557088
doi:
Types de publication
Journal Article
Langues
eng
Pagination
35-44Commentaires et corrections
Type : CommentIn
Informations de copyright
Crown Copyright © 2022 Published by Elsevier B.V. on behalf of European Association of Urology.
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