B7-H1-dependent sex-related differences in tumor immunity and immunotherapy responses.
B7-H1-dependent sex-related differences in tumor immunity and immunotherapy responses.
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DOI：
10.4049/jimmunol.1000496
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Curiel TJ
中科院分区：
文献类型：
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作者：
Lin PY;Sun L;Thibodeaux SR;Ludwig SM;Vadlamudi RK;Hurez VJ;Bahar R;Kious MJ;Livi CB;Wall SR;Chen L;Zhang B;Shin T;Curiel TJ
CD 4 + CD 25 + Foxp 3+调节性T细胞（TCRs）通过阻碍肿瘤特异性免疫而在癌症中是免疫致病性的。B7同源物1（B7-H1）（CD 274）是一种具有多效性的共信号分子，包括阻碍抗肿瘤免疫。在这项研究中，我们证明了性别依赖性，B7-H1依赖性的肿瘤免疫和免疫治疗的反应在非肿瘤依赖性癌症，小鼠B16黑色素瘤的差异。由于B7-H1 −/−女性中调节性T细胞功能降低，B7-H1 −/−女性的抗肿瘤免疫性优于男性，并且由于B7-H1阻断介导的Treg功能降低更大，野生型女性中B7-H1阻断作为肿瘤免疫治疗后的临床应答显著优于男性。野生型女性Tendon表达显着低于男性B7-H1，但在体外对雌激素不敏感。雌性B7-H1−/− Treg在体外对雌激素介导的功能降低非常敏感，表明B7-H1效应发生在终末Treg分化之前。免疫差异独立于已知的B7-H1配体。在设计免疫疗法或解释免疫疗法治疗结果时很少考虑性别依赖性免疫差异。我们的数据表明，性别是肿瘤免疫发病机制和免疫治疗反应的一个重要变量，通过不同的Treg功能和B7-H1信号传导。
CD4+CD25+Foxp3+ regulatory T cells (Tregs) are immunopathogenic in cancers by impeding tumor-specific immunity. B7-homologue 1 (B7-H1) (CD274) is a cosignaling molecule with pleiotropic effects, including hindering antitumor immunity. In this study, we demonstrate sex-dependent, B7-H1–dependent differences in tumor immunity and response to immunotherapy in a hormone-independent cancer, murine B16 melanoma. Antitumor immunity was better in B7-H1−/− females versus males as a result of reduced regulatory T cell function in the B7-H1−/− females, and clinical response following B7-H1 blockade as tumor immunotherapy was significantly better in wild-type females than in males, owing to greater B7-H1 blockade-mediated reduction of Treg function in females. Wild-type female Tregs expressed significantly lower B7-H1 versus males but were insensitive to estrogen in vitro. Female B7-H1−/− Tregs were exquisitely sensitive to estrogen-mediated functional reduction in vitro, suggesting that B7-H1 effects occur before terminal Treg differentiation. Immune differences were independent of known B7-H1 ligands. Sex-dependent immune differences are seldom considered in designing immune therapy or interpreting immunotherapy treatment results. Our data demonstrate that sex is an important variable in tumor immunopathogenesis and immunotherapy responses through differential Treg function and B7-H1 signaling.
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DOI：
10.1038/nri2394
发表时间：
2008-09
期刊：
Nature reviews. Immunology
影响因子：
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作者：
Fish EN
通讯作者：
Fish EN
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
20.3
作者：
Litzinger, Mary T.;Fernando, Romaine;Palena, Claudia
通讯作者：
Palena, Claudia
影响因子：
32.4
作者：
Butte, Manish J.;Keir, Mary E.;Freeman, Gordon J.
通讯作者：
Freeman, Gordon J.
影响因子：
82.9
作者：
通讯作者：
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