Role of neutrophils in BCG immunotherapy for bladder cancer
Role of neutrophils in BCG immunotherapy for bladder cancer
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DOI：
10.1016/j.urolonc.2007.11.031
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发表时间：
2008-07-01
影响因子：
2.7
通讯作者：
Griffith, Thomas S.
中科院分区：
文献类型：
--
作者：
Simons, Mark P.;O'Donnell, Michael A.;Griffith, Thomas S.
膀胱癌每年约有13，000人死亡，今年将出现超过60，000例新病例，使其分别成为男性和女性中第四和第十大最常见的癌症[1]。大多数新诊断的病例将在肌肉浸润之前被诊断出来，因此可能完全治愈。不幸的是，>20%的最初诊断为非肌层浸润性膀胱癌的患者最终会死于他们的疾病，尽管进行了局部内窥镜手术[2]。自1976年以来，牛分枝杆菌卡介苗（BCG）已用于治疗膀胱癌[3]，并继续处于这种恶性肿瘤治疗选择的最前沿。尽管它的成功和世界范围内的接受，抗肿瘤效应机制仍然难以捉摸。BCG治疗诱导大量局部免疫应答，其特征在于尿液和膀胱组织中多种细胞因子的表达[4]，以及粒细胞和单核细胞流入膀胱壁[5，6]。我们实验室的研究结果表明，肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）是由BCG治疗诱导的[7]，并且TRAIL在膀胱内灌注BCG后患者尿液中的多形核中性粒细胞（PMN）上表达。随后，我们已经确定BCG和分枝杆菌细胞壁的组分可以通过干扰素（IFN）增强的toll样受体-2（TLR 2）识别直接刺激可溶性TRAIL从PMN释放[8]。基于我们的工作和其他人暗示需要T辅助细胞1型（Th-1）细胞因子反应BCG治疗的治疗结果，我们建议，释放TRAIL的PMN迁移到膀胱BCG治疗。此外，IFN的作用是增加和延长由PMN释放的TRAIL的量，导致有效的治疗结果。(C)2008年爱思唯尔公司All rights reserved.
Bladder cancer accounts for similar to 13,000 deaths annually, and >60,000 new cases will appear this year, making it the fourth and tenth most common cancer among men and women, respectively [1]. The majority of the newly diagnosed cases will be diagnosed prior to muscle invasion, and are thus potentially completely curable. Unfortunately, >20% of patients initially diagnosed with non-muscle invasive bladder cancer will eventually die of their disease despite local endoscopic surgery [2]. Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used for the treatment of bladder cancer since 1976 [3], and continues to be at the forefront of therapeutic options for this malignancy. Despite its success and worldwide acceptance, the antitumor effector mechanisms remain elusive. BCG therapy induces a massive local immune response characterized by the expression of multiple cytokines in the urine and bladder tissue [4], and the influx of granulocytes and mononuclear cells into the bladder wall [5,6]. Findings from our laboratory have demonstrated that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is induced by BCG treatment [7], and TRAIL was expressed on poly morphonuclear neutrophils (PMN) in the urine obtained from patients after intravesical BCG instillation. Subsequently, we have determined that BCG and components of the mycobacterial cell wall can directly stimulate the release of soluble TRAIL from PMN through toll-like receptor-2 (TLR2) recognition that is augmented by interferon (IFN) [8]. Based on our work and that of others implicating the need for T helper type 1 (Th-1) cytokine responses to BCG therapy for therapeutic results, we propose that TRAIL is released by PMN migrating to the bladder in response to BCG treatment. In addition, IFN acts to augment and prolong the amount of TRAIL released by PMN, resulting in an effective therapeutic outcome. (C) 2008 Elsevier Inc. All rights reserved.