The tumor microenvironment: a target for combination therapy of breast cancer.
The tumor microenvironment: a target for combination therapy of breast cancer.
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DOI：
10.1615/critrevoncog.v18.i1-2.70
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发表时间：
2013
影响因子：
--
通讯作者：
R. Reisfeld
中科院分区：
文献类型：
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作者：
R. Reisfeld
癌症免疫治疗正处于一个重大的范式转变中，从主要专注于攻击肿瘤细胞的方法转向也针对肿瘤微环境(TME)的策略。这一策略是为联合疗法的使用而设计的，这里回顾了几种联合疗法。特别强调针对TME的这样的组件，如肿瘤相关巨噬细胞(TAMs)和癌症相关成纤维细胞(CAF)，它们分别表达特定的治疗靶点，如Legumain、天冬酰胺内肽酶、原癌基因Fra-1、转录因子STAT3和成纤维细胞激活蛋白(FAP)以及HER-2。在小鼠肿瘤模型中，针对其中一些在乳腺肿瘤细胞以及TAMs和CAF上过度表达的靶点的DNA疫苗的使用，可以消除肿瘤的生长、进展、转移和复发。通过一种专门设计的策略将包括DNA疫苗在内的免疫疗法与一种新型化疗相结合，显著提高了这种类型的癌症治疗的疗效，这种新型化疗具有高效的纳米颗粒介导的药物输送，专门针对肿瘤细胞以及TME的关键成分，导致其调节和随后消除肿瘤的生长、转移，最重要的是，抑制肿瘤的复发。
Cancer immunotherapy is in the midst of a major paradigm shift from an approach primarily focused on attacking tumor cells to a strategy also targeting the tumor microenvironment (TME). This strategy is designed for the use of combination therapies, several of which are reviewed here. Particular emphasis is placed on targeting such components of the TME as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) overexpressing specific therapy targets such as Legumain, an asparaginyl endopeptidase, proto-oncogene Fra-1, transcription factor Stat3 and fibroblast activation protein (FAP) as well as HER-2, respectively. The use of DNA vaccines directed against some of these targets overexpressed on both breast tumor cells as well as TAMs and CAFs in the TME results in the elimination of tumor growth, progression, metastasis and recurrence in mouse tumor models. This type of cancer therapy is significantly improved in efficacy by a strategy specifically designed to combine immunotherapies, including DNA vaccines, with a novel chemotherapy featuring highly effective nanoparticle-mediated drug delivery, specifically targeted to tumor cells as well as key components of the TME, leading to its modulation and subsequent elimination of tumor growth, metastasis, and, most importantly, suppression of tumor recurrence.