The Superior Ability of Human BDCA3+(CD141+) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells
The Superior Ability of Human BDCA3+(CD141+) Dendritic Cells (DCs) to Cross-Present Antigens Derived From Necrotic Lung Cancer Cells
复制标题
人 BDCA3( )(CD141( )) 树突状细胞 (DC) 交叉存在来自坏死肺癌细胞的抗原的卓越能力
DOI：
10.3389/fimmu.2020.01267
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发表时间：
2020-06-19
影响因子：
7.3
通讯作者：
Liu, Li
中科院分区：
文献类型：
--
作者：
Gu, Fei-fei;Zhang, Kai;Liu, Li
树突状细胞（Dendritic cells，DC）在启动和调节针对病原体、自身抗原和癌症的免疫应答中起关键作用。人血DC包括一个不同亚群的家族：浆细胞样DC（pDC）和CD 16（+）、CD 1c/BDCA 1（+）和BDCA 3（+）（CD 141（+））髓样DC，并且具有不同的表型和功能特征。肺癌是世界上发病率和死亡率最高的恶性肿瘤。然而，哪个DC亚群在肺癌免疫应答中起主导作用尚不清楚。我们重新分析了癌症基因组图谱（TCGA）数据库中的C型凝集素结构域家族9成员A（CLEC 9A）和CD 141（THBD）基因表达谱，并根据其表达水平对几种癌症的总生存率进行了Kaplan-Meier生存分析。接下来，我们研究了五种人血DC亚群刺激T细胞增殖和捕获、加工和（交叉）呈递肿瘤抗原的能力。人BDCA 3（+）（CD 141（+））DC与其他DC亚群相比具有上级刺激同种异体CD 4（+）T细胞增殖和诱导上级Th 1应答的能力。有趣的是，Toll样受体（TLR）激动剂对DC诱导幼稚CD 4（+）T细胞增殖的作用很小，但有助于其分化。重要的是，BDCA 3（+）（CD 141（+））DC在摄取坏死的肺癌细胞后具有最有效的交叉呈递人肿瘤抗原的能力，尽管它们的抗原摄取较低。这些发现表明，人BDCA 3（+）（CD 141（+））DC是细胞毒性T淋巴细胞对EGFR阳性肺癌反应的关键介质。本研究为DC为基础的抗肿瘤疫苗的研制提供了理论依据。
Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16(+), CD1c/BDCA1(+), and BDCA3(+)(CD141(+)) myeloid DCs and possess different phenotypes and functional characteristics. Lung cancer is the most common cancer, with the highest morbidity and mortality in the world. However, which DC subset plays a leading role in the lung cancer immune responses is unclear. We reanalyzed C-type lectin domain family 9 member A (CLEC9A) and CD141 (THBD) gene expression profiles from the Cancer Genome Atlas (TCGA) database and performed the Kaplan-Meier survival analysis of overall survival for several cancers according to their expression levels. Next, we investigated the capacities of five human blood DC subsets to stimulate T cell proliferation and capture, process and (cross-) present tumor antigen. Human BDCA3(+)(CD141(+)) DCs have a superior capacity to stimulate allogeneic CD4(+)T cells proliferation and induce superior Th1 response compared with other DC subsets. Interestingly, toll-like receptor (TLR) agonists have little effect on DCs to induce the proliferation of naive CD4(+)T cells, but contribute to their differentiation. Importantly, BDCA3(+)(CD141(+)) DCs possess the most potent ability to cross-present human tumor antigen after their uptake of necrotic lung cancer cells despite their lower antigen uptake. These findings suggest that human BDCA3(+)(CD141(+)) DCs are critical mediators of cytotoxic T lymphocyte responses against EGFR-positive lung cancer. Therefore, our findings may provide theoretical basis for the development of DC-based antitumor vaccines.