Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma.
Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma.
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DOI：
10.3389/fimmu.2017.01594
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发表时间：
2017
影响因子：
7.3
通讯作者：
Hargadon KM
中科院分区：
文献类型：
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作者：
Hargadon KM
黑色素瘤是一种高度侵袭性的皮肤癌，经常转移到重要器官，通常难以用手术和放射等传统疗法治疗。在这种转移性疾病的情况下，免疫疗法近年来已成为黑色素瘤患者令人兴奋的治疗选择。尽管免疫治疗在临床上取得了前所未有的成功，但许多患者仍然会出现疾病复发，而其他患者则根本没有反应，因此需要更好地了解影响抗肿瘤免疫反应疗效的因素。抗肿瘤免疫的核心是树突状细胞（DC），这是一种先天性细胞群，作为免疫耐受和激活的关键调节因子发挥作用。因此，DC具有作为癌症免疫治疗的重要靶标和递送剂的潜力。即使是不直接靶向或使用DC的免疫疗法，如检查点阻断疗法和过继细胞转移疗法，也可能依赖于塑造治疗相关抗肿瘤免疫质量的DC。因此，了解调节肿瘤相关DC功能的因素对于优化当前和未来治疗黑色素瘤的免疫策略至关重要。为此，本文综述了我们对黑色素瘤背景下DC功能的理解进展，特别强调（1）免疫原性细胞死亡在引发肿瘤相关DC激活中的作用，（2）肿瘤微环境中黑色素瘤相关因子对DC功能的免疫抑制，（3）肿瘤相关DC激活的代谢约束，和（4）微生物组在形成DC的免疫原性和它们介导的抗黑素瘤免疫应答的总体质量中的作用。此外，这篇综述强调了新的基于DC的黑色素瘤免疫疗法，这些免疫疗法是从这些研究领域的最新进展中出现的，并讨论了当前的问题和未来研究中需要解决的问题，这些研究旨在优化黑色素瘤相关DC的功能和它们针对这种癌症的抗肿瘤免疫反应。
Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment option for melanoma patients. Despite unprecedented successes with immune therapy in the clinic, many patients still experience disease relapse, and others fail to respond at all, thus highlighting the need to better understand factors that influence the efficacy of antitumor immune responses. At the heart of antitumor immunity are dendritic cells (DCs), an innate population of cells that function as critical regulators of immune tolerance and activation. As such, DCs have the potential to serve as important targets and delivery agents of cancer immunotherapies. Even immunotherapies that do not directly target or employ DCs, such as checkpoint blockade therapy and adoptive cell transfer therapy, are likely to rely on DCs that shape the quality of therapy-associated antitumor immunity. Therefore, understanding factors that regulate the function of tumor-associated DCs is critical for optimizing both current and future immunotherapeutic strategies for treating melanoma. To this end, this review focuses on advances in our understanding of DC function in the context of melanoma, with particular emphasis on (1) the role of immunogenic cell death in eliciting tumor-associated DC activation, (2) immunosuppression of DC function by melanoma-associated factors in the tumor microenvironment, (3) metabolic constraints on the activation of tumor-associated DCs, and (4) the role of the microbiome in shaping the immunogenicity of DCs and the overall quality of anti-melanoma immune responses they mediate. Additionally, this review highlights novel DC-based immunotherapies for melanoma that are emerging from recent progress in each of these areas of investigation, and it discusses current issues and questions that will need to be addressed in future studies aimed at optimizing the function of melanoma-associated DCs and the antitumor immune responses they direct against this cancer.