Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma
Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma
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DOI：
10.1093/carcin/bgz124
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发表时间：
2020-05-01
期刊：
影响因子：
4.7
通讯作者：
Whiteside, Theresa L.
中科院分区：
文献类型：
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作者：
Razzo, Beatrice M.;Ludwig, Nils;Whiteside, Theresa L.
循环中的肿瘤衍生外切体(TeX)与荷癌宿主中的各种细胞相互作用，导致细胞重新编程，从而促进疾病的进展。为了研究TeX对实体瘤发生发展的影响，从小鼠和人HNSCC细胞上清液中分离出携带PD-L1和FasL的免疫抑制外切体。给免疫活性C57BL/6小鼠注射4-硝基喹啉-1-氧化物(4NQO)诱发的口腔/食道癌前病变。监测口咽癌前病变向恶性肿瘤的进展情况。一次TeX注射增加了发展中的肿瘤数量(注射磷酸盐缓冲盐水的对照组为6.2vs.3.2；P<；0.0002)和每只小鼠的总肿瘤负担(P<；0.037)。与对照组相比，注射SCCVII来源的TeX的小鼠的CD4(+)和CD8(+)T淋巴细胞数量协同减少(P<；0.01)。值得注意的是，从小鼠或人类肿瘤中分离出来的TeX对肿瘤的发展和免疫细胞也有类似的影响。一次静脉注射TeX就足以使患有癌前口腔鳞癌病变的小鼠在肿瘤进展加速的同时减少免疫细胞向肿瘤的迁移。
Circulating tumor-derived exosomes (TEX) interact with a variety of cells in cancer-bearing hosts, leading to cellular reprogramming which promotes disease progression. To study TEX effects on the development of solid tumors, immunosuppressive exosomes carrying PD-L1 and FasL were isolated from supernatants of murine or human HNSCC cell lines. TEX were delivered (IV) to immunocompetent C57BL/6 mice bearing premalignant oral/esophageal lesions induced by the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Progression of the premalignant oropharyngeal lesions to malignant tumors was monitored. A single TEX injection increased the number of developing tumors (6.2 versus 3.2 in control mice injected with phosphate-buffered saline; P < 0.0002) and overall tumor burden per mouse (P < 0.037). The numbers of CD4(+) and CD8(+) T lymphocytes infiltrating the developing tumors were coordinately reduced (P < 0.01) in mice injected with SCCVII-derived TEX relative to controls. Notably, TEX isolated from mouse or human tumors had similar effects on tumor development and immune cells. A single IV injection of TEX was sufficient to condition mice harboring premalignant OSCC lesions for accelerated tumor progression in concert with reduced immune cell migration to the tumor.