Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.
Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.
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DOI：
10.1158/0008-5472.1089.65.3
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发表时间：
2005-02
期刊：
影响因子：
11.2
通讯作者：
F. Hirano;K. Kaneko;H. Tamura;Haidong Dong;Shengdian Wang;Masao Ichikawa;C. Rietz;D. Flies
中科院分区：
文献类型：
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作者：
F. Hirano;K. Kaneko;H. Tamura;Haidong Dong;Shengdian Wang;Masao Ichikawa;C. Rietz;D. Flies
现代疫苗接种和免疫治疗方法通常能够引发针对肿瘤抗原的强烈 T 细胞反应。然而，这种反应与临床肿瘤消退并不平行。肿瘤微环境中逃避机制的发展可能是治疗反应不佳的原因。我们在此报告，B7-H1（一种在癌症中广泛表达的 B7 家族分子）的组成型或诱导型表达赋予已形成肿瘤的小鼠对治疗性抗 CD137 抗体的抵抗力。这种耐药性伴随着抗原特异性 CD8+ CTL 无法在不损害 CTL 功能的情况下破坏肿瘤细胞。通过特异性单克隆抗体阻断 B7-H1 或 PD-1 可以逆转这种耐药性并显着提高治疗效果。我们的研究结果支持 B7-H1/PD-1 形成分子盾来防止 CTL 的破坏，并暗示人类癌症免疫治疗的新方法。
Contemporary approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, such responses are not parallel to clinical tumor regression. The development of evasion mechanisms within tumor microenvironment may be responsible for poor therapeutic responses. We report here that constitutive or inducible expression of B7-H1, a B7 family molecule widely expressed by cancers, confers resistance to therapeutic anti-CD137 antibody in mice with established tumors. The resistance is accompanied with failure of antigen-specific CD8+ CTLs to destroy tumor cells without impairment of CTL function. Blockade of B7-H1 or PD-1 by specific monoclonal antibodies could reverse this resistance and profoundly enhance therapeutic efficacy. Our findings support that B7-H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers.