Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
1.33, Hillman Cancer Center, University of Pittsburgh, PA 15213, USA.
Crit Rev Oncol Hematol. 2016 Nov;107:100-110. doi: 10.1016/j.critrevonc.2016.09.002. Epub 2016 Sep 9.
Better prognoses associated with increased T cell infiltration of tumors, as seen with chimeric antigen receptor (CAR) T cell therapies and immune checkpoint inhibitors, portray the importance and potential of the immune system in controlling tumors. This has rejuvenated the field of cancer immunotherapy leading to an increasing number of immunotherapies developed for cancer patients. Dendritic Cells (DCs) vaccines represent an appealing option for cancer immunotherapy since DCs have the ability to circumvent tolerance to tumors by its adjuvant properties and to induce memory T cells that can become persistent after initial tumor clearance to engage potential metastatic tumors. In the past, DC-based cancer vaccines have elicited only poor clinical response in cancer patients, which can be attributed to complex and a multitude of issues associated with generation, implementing, delivery of DC vaccine and their potential interaction with effector cells. The current review mainly focuses on migration/trafficking of DCs, as one of the key issues that affect the success of DC-based cancer vaccines, and discusses strategies to enhance it for cancer immunotherapy. Additionally, impact of maturation, route of DC delivery and negative effects of tumor microenvironment (TME) on DC homing to LN are reviewed. Moreover, strategies to increase the expression of genes involved in Lymph node homing, preconditioning of the vaccination site, enhancing lymph node ability to attract and receive DCs, while limiting negative impact of TME on DC migration are discussed.
肿瘤中 T 细胞浸润增加与更好的预后相关，这在嵌合抗原受体 (CAR) T 细胞疗法和免疫检查点抑制剂中可见一斑，这凸显了免疫系统在控制肿瘤方面的重要性和潜力。这使得癌症免疫疗法领域焕发生机，越来越多的免疫疗法被开发用于癌症患者。树突状细胞 (DC) 疫苗是癌症免疫疗法的一个有吸引力的选择，因为 DC 具有通过其佐剂特性绕过对肿瘤的耐受性的能力，并诱导可以在初始肿瘤清除后持续存在的记忆 T 细胞，以参与潜在的转移性肿瘤。过去，基于 DC 的癌症疫苗在癌症患者中仅引起了较差的临床反应，这可以归因于与生成、实施、递送 DC 疫苗及其与效应细胞的潜在相互作用相关的复杂和众多问题。目前的综述主要集中在 DC 的迁移/运输上，这是影响基于 DC 的癌症疫苗成功的关键问题之一，并讨论了增强其用于癌症免疫疗法的策略。此外，还综述了成熟、DC 递送途径和肿瘤微环境 (TME) 对 DC 归巢到 LN 的负面影响的影响。此外，还讨论了增加参与淋巴结归巢的基因表达的策略、接种部位的预处理、增强淋巴结吸引和接收 DC 的能力，同时限制 TME 对 DC 迁移的负面影响。
