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BAM-SiPc介导的血管光动力疗法在BALB/c小鼠模型中的抗肿瘤免疫

Anti-tumor immunity of BAM-SiPc-mediated vascular photodynamic therapy in a BALB/c mouse model.

作者信息

Yeung Hing-Yuen, Lo Pui-Chi, Ng Dennis K P, Fong Wing-Ping

机构信息

School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

出版信息

Cell Mol Immunol. 2017 Feb;14(2):223-234. doi: 10.1038/cmi.2015.84. Epub 2015 Sep 21.

Abstract

In recent decades, accumulating evidence from both animal and clinical studies has suggested that a sufficiently activated immune system may strongly augment various types of cancer treatment, including photodynamic therapy (PDT). Through the generation of reactive oxygen species, PDT eradicates tumors by triggering localized tumor damage and inducing anti-tumor immunity. As the major component of anti-tumor immunity, the involvement of a cell-mediated immune response in PDT has been well investigated in the past decade, whereas the role of humoral immunity has remained relatively unexplored. In the present investigation, using the photosensitizer BAM-SiPc and the CT26 tumor-bearing BALB/c mouse model, it was demonstrated that both cell-mediated and humoral adaptive immune components could be involved in PDT. With a vascular PDT (VPDT) regimen, BAM-SiPc could eradicate the tumors of ∼70% of tumor-bearing mice and trigger an anti-tumor immune response that could last for more than 1 year. An elevation of Th2 cytokines was detected ex vivo after VPDT, indicating the potential involvement of a humoral response. An analysis of serum from the VPDT-cured mice also revealed elevated levels of tumor-specific antibodies. Moreover, this serum could effectively hinder tumor growth and protect the mice against further re-challenge in a T-cell-dependent manner. Taken together, these results show that the humoral components induced after BAM-SiPc-VPDT could assist the development of anti-tumor immunity.

摘要

近几十年来,动物和临床研究积累的证据表明,充分激活的免疫系统可能会显著增强包括光动力疗法(PDT)在内的各种癌症治疗效果。通过产生活性氧,PDT通过引发局部肿瘤损伤和诱导抗肿瘤免疫来根除肿瘤。作为抗肿瘤免疫的主要组成部分,细胞介导的免疫反应在PDT中的作用在过去十年中已得到充分研究,而体液免疫的作用仍相对未被探索。在本研究中,使用光敏剂BAM-SiPc和荷CT26肿瘤的BALB/c小鼠模型,证明细胞介导和体液适应性免疫成分均可参与PDT。采用血管靶向光动力疗法(VPDT)方案,BAM-SiPc可根除约70%荷瘤小鼠的肿瘤,并引发可持续1年以上的抗肿瘤免疫反应。VPDT后体外检测到Th2细胞因子升高,表明可能涉及体液反应。对VPDT治愈小鼠血清的分析还显示肿瘤特异性抗体水平升高。此外,这种血清可以有效地抑制肿瘤生长,并以T细胞依赖的方式保护小鼠免受进一步的再攻击。综上所述,这些结果表明,BAM-SiPc-VPDT后诱导的体液成分可以辅助抗肿瘤免疫的发展。

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