Varney Michelle L, Singh Seema, Backora Matthew, Chen Zhengtang, Singh Rakesh K
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5845, USA.
Curr Mol Med. 2009 Aug;9(6):694-701. doi: 10.2174/156652409788970733.
Tumor-induced immunosuppression is a fundamental problem in cancer immunotherapy and can occur by a variety of cellular and molecular mechanisms, affecting all arms of the immune system. Tumor-produced or elicited factors have been shown to inhibit antigen-specific immune effector function as well as impairment of the development, recruitment and maturation of dendritic cells (DCs) and T cells. A better understanding of the cross-talk between tumors and tumor-associated DCs and T cells is necessary to develop novel approaches for cancer immunotherapy. The recruitment of DCs to tumors, antigen processing and presentation, and migration of antigen-loaded DCs to secondary lymphoid organs are perturbed in tumor-bearing hosts. The ability of tumor-associated DCs to induce an anti-tumor response may be prevented by the tumor microenvironment due to inhibitory factors such as vascular endothelial growth factor (VEGF)-C, which are also known to regulate tumor angiogenesis and lymphangiogenesis. Strategies to inhibit tumor-induced angiogenesis and immunosuppression provide therapeutic approaches with the potential for synergism. In this review we will discuss the possibilities of developing novel approaches to concurrently inhibit angiogenesis, inhibit lymphangiogenesis, eliminate tumor-induced immunosuppression and augment the anti-tumor immune as potent multi-modality therapeutic strategies for metastatic cancer.
肿瘤诱导的免疫抑制是癌症免疫治疗中的一个基本问题，可通过多种细胞和分子机制发生，影响免疫系统的各个方面。肿瘤产生或引发的因子已被证明可抑制抗原特异性免疫效应功能，以及损害树突状细胞（DC）和T细胞的发育、募集和成熟。为了开发癌症免疫治疗的新方法，有必要更好地理解肿瘤与肿瘤相关DC和T细胞之间的相互作用。在荷瘤宿主中，DC向肿瘤的募集、抗原处理和呈递以及负载抗原的DC向次级淋巴器官的迁移均受到干扰。肿瘤微环境可能会因血管内皮生长因子（VEGF）-C等抑制因子而阻止肿瘤相关DC诱导抗肿瘤反应，这些抑制因子也已知可调节肿瘤血管生成和淋巴管生成。抑制肿瘤诱导的血管生成和免疫抑制的策略提供了具有协同作用潜力的治疗方法。在本综述中，我们将讨论开发新方法的可能性，这些新方法可同时抑制血管生成、抑制淋巴管生成、消除肿瘤诱导的免疫抑制并增强抗肿瘤免疫，作为转移性癌症的有效多模态治疗策略。
