Department of Medicine, NYU Langone Medical Center, New York, NY, USA.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Carcinogenesis. 2020 Jul 10;41(5):625-633. doi: 10.1093/carcin/bgz124.
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.
循环肿瘤衍生的外泌体 (TEX) 与癌症宿主中的多种细胞相互作用，导致细胞重编程，从而促进疾病进展。为了研究 TEX 对实体瘤发展的影响，从鼠源性或人源性头颈部鳞状细胞癌 (HNSCC) 细胞系的上清液中分离出携带 PD-L1 和 FasL 的免疫抑制性外泌体。将 TEX（IV 注射）递送至携带由致癌剂 4-硝基喹啉 1-氧化物 (4NQO) 诱导的癌前口腔/食管病变的免疫活性 C57BL/6 小鼠体内。监测癌前口咽病变向恶性肿瘤的进展。单次 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 6.2 个，而注射 TEX 的组为 6.2 个；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 衍生的 TEX 的小鼠中浸润发展中的肿瘤的 CD4+和 CD8+T 淋巴细胞数量协同减少（P < 0.01）。值得注意的是，从鼠源性或人源性肿瘤中分离出的 TEX 对肿瘤发展和免疫细胞具有相似的影响。单次 IV 注射 TEX 足以使携带癌前 OSCC 病变的小鼠对肿瘤的加速进展进行调理，同时减少免疫细胞向肿瘤的迁移。
