Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma

Razzo, Beatrice M., Nils Ludwig, Chang-Sook Hong, Priyanka Sharma, Kellsye P. Fabian, Ronald J. Fecek, Walter J. Storkus, and Theresa L. Whiteside. "Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma." Carcinogenesis (2019).

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 pre-malignant 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 vs 3.2 in control mice injected with PBS; 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 pre-malignant OSCC lesions for accelerated tumor progression in concert with reduced immune cell migration to the tumor.

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