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首页> 外文期刊>Cellular immunology >Efficient induction of anti-tumor immune response in esophageal squamous cell carcinoma via dendritic cells expressing MAGE-A3 and CALR antigens
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Efficient induction of anti-tumor immune response in esophageal squamous cell carcinoma via dendritic cells expressing MAGE-A3 and CALR antigens

机译：通过表达MAGE-A3和CALR抗原的树突状细胞有效诱导食管鳞状细胞癌抗肿瘤免疫反应

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摘要

Despite advances in the various treatment options for esophageal squamous cell carcinoma (ESCC), its prognosis is still very poor with a 5-year survival rate of only 14-22%. Recently, among the various therapeutic approaches, the focus has shifted to immunotherapy, specifically immunotherapy involving dendritic cells (DCs), which depends on their maturation and antigen presentation to effector immune cells. Recent studies have suggested that melanoma-associated antigen 3 (MAGE-A3) is a potential immunotherapeutic target and also a candidate for the development of an anti-tumor vaccine. Calreticulin (CALR) has been shown to support induction of DC maturation. Therefore, in this study, we overexpressed MAGE-A3 and CALR on DCs and studied their potential to generate anti-tumor immune responses. We observed that adenovirus (Ad)-infected DCs overexpressing CALR and MAGE-A3 showed enhanced expression of CD80, CD83, CD86, and HLA-DR markers. Also, these DCs secreted higher levels of interleukin (IL)-12, which induces the T helper type 1 cell (Th1) response, and a lower level of IL-10, a negative regulator of the Th1 response. Furthermore, CALR/MAGE-A3-infected DCs stimulated CD8(+) cytotoxic T lymphocytes, which in turn secreted higher levels of interferon-gamma, which induced cytotoxic effects on ESCC cells expressing MAGE-A3. In conclusion, our results revealed the potential of CALR/MAGE-A3-infected DCs to elicit a MAGE-A3-specific anti-tumor immunogenic response in ESCC. This proof-of-principle study may promote the future design and development of DC-based effective immunotherapy against ESCC. (C) 2015 Elsevier Inc. All rights reserved.
机译：尽管食管鳞状细胞癌（ESCC）的各种治疗选择都有进展，但其预后仍然很差，其5年生存率仅为14-22％。近来，在各种治疗方法中，焦点已经转移到免疫疗法，特别是涉及树突状细胞（DC）的免疫疗法，这取决于它们的成熟和向效应物免疫细胞的抗原呈递。最近的研究表明，黑素瘤相关抗原3（MAGE-A3）是潜在的免疫治疗靶标，也是开发抗肿瘤疫苗的候选者。钙网蛋白（CALR）已显示支持DC成熟。因此，在这项研究中，我们在DC上过表达了MAGE-A3和CALR，并研究了它们产生抗肿瘤免疫应答的潜力。我们观察到过度表达CALR和MAGE-A3的腺病毒（Ad）感染的DC显示出CD80，CD83，CD86和HLA-DR标记的增强表达。而且，这些DC分泌较高水平的白介素（IL）-12，从而诱导T辅助1型细胞（Th1）反应，而分泌较低水平的IL-10，即Th1反应的负调节剂。此外，CALR / MAGE-A3感染的DC刺激CD8（+）细胞毒性T淋巴细胞，进而分泌更高水平的干扰素-γ，从而对表达MAGE-A3的ESCC细胞诱导细胞毒性作用。总之，我们的结果揭示了感染CALR / MAGE-A3的DC在ESCC中引发MAGE-A3特异性抗肿瘤免疫原性应答的潜力。这项原理验证研究可能会促进基于DC的抗ESCC有效免疫疗法的未来设计和开发。 （C）2015 Elsevier Inc.保留所有权利。

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