IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.
IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.
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DOI：
10.1038/s41586-018-0266-0
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发表时间：
2018-07
期刊：
影响因子：
64.8
通讯作者：
Alimonti A
中科院分区：
文献类型：
--
作者：
Calcinotto A;Spataro C;Zagato E;Di Mitri D;Gil V;Crespo M;De Bernardis G;Losa M;Mirenda M;Pasquini E;Rinaldi A;Sumanasuriya S;Lambros MB;Neeb A;Lucianò R;Bravi CA;Nava-Rodrigues D;Dolling D;Prayer-Galetti T;Ferreira A;Briganti A;Esposito A;Barry S;Yuan W;Sharp A;de Bono J;Alimonti A
前列腺癌患者经常对雄激素剥夺治疗（ADT）产生耐药性。更好地了解控制去势抵抗性前列腺癌（CRPC）发展的机制仍然是一个未满足的临床需求。癌细胞对肿瘤微环境的依赖性表明它可能控制CRPC的出现。在这里，我们确定骨髓来源的抑制细胞（MDSC）产生的IL 23作为CRPC的驱动程序。从机制上讲，MDSC分泌的IL 23可以激活前列腺肿瘤细胞中的雄激素受体途径，促进雄激素剥夺条件下的细胞存活和增殖。肿瘤内MDSC浸润和IL 23浓度在CRPC患者的血液和肿瘤样品中增加。抗体介导的IL23失活恢复了小鼠对ADT的敏感性。总之，这些结果表明，MDSC通过以非细胞自主方式起作用来促进CRPC。阻断IL 23的治疗可以对抗MDSC介导的去势抵抗，并与标准护理疗法协同作用。
Prostate cancer patients frequently experience resistance to androgen deprivation therapy (ADT). Acquiring a better understanding of the mechanisms controlling the development of castration resistant prostate cancer (CRPC) remains an unmet clinical need. The well-established dependency of cancer cells on the tumor microenvironment suggests that it might control the emergence of CRPC. Here, we identify IL23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC. Mechanistically, IL23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumor cells, promoting cell survival and proliferation in androgen deprived conditions. Intra-tumor MDSC infiltration, and IL23 concentration, increases in the blood and tumor samples of CRPC patients. Antibody-mediated inactivation of IL23 restored sensitivity to ADT in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL23 can oppose MDSC-mediated castration resistance and synergize with standard of care therapies.
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DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.7
作者：
Lee, Geun Taek;Jung, Yeon Suk;Kim, Isaac Y.
通讯作者：
Kim, Isaac Y.
DOI：
10.1158/1078-0432.ccr-14-3145
发表时间：
2015-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hossain DM;Pal SK;Moreira D;Duttagupta P;Zhang Q;Won H;Jones J;D'Apuzzo M;Forman S;Kortylewski M
通讯作者：
Kortylewski M
影响因子：
14.8
作者：
Drost J;Karthaus WR;Gao D;Driehuis E;Sawyers CL;Chen Y;Clevers H
通讯作者：
Clevers H