恩扎鲁胺
免疫疗法
医学
免疫系统
膀胱癌
前列腺癌
癌症研究
癌症
雄激素受体
肿瘤科
抗雄激素
体内
杜瓦卢马布
内科学
免疫学
生物
彭布罗利珠单抗
生物技术
作者
Marjorie Besançon,Typhaine Gris,France‐Hélène Joncas,Valérie Picard,Alain Bergeron,Yves Fradet,Paul Toren
标识
DOI:10.1016/j.euros.2022.06.007
摘要
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. In vivo 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.Tumor growth and survival were evaluated in vivo. 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.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.
科研通智能强力驱动
Strongly Powered by AbleSci AI