Sumi Shigeki, Umemura Naoki, Takayama Eiji, Ohkoshi Emika, Adachi Makoto, Mizuno-Kamiya Masako, Inagaki Toshihiro, Kawaki Harumi, Sumitomo Shinichiro, Kondoh Nobuo
Department of Oral and Maxillofacial Surgery, Asahi University School of Dentistry, Gifu 501‑0296, Japan.
Department of Oral Biochemistry, Asahi University School of Dentistry, Gifu 501‑0296, Japan.
Oncol Rep. 2017 May;37(5):2897-2904. doi: 10.3892/or.2017.5575. Epub 2017 Apr 11.
Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and peripheral blood during inflammation or tumor tissues and lymph nodes in the presence of a tumor. However, whether there are differences in MDSCs found in the primary tumor and metastases is unknown. In the present study, we established a cell line of metastasized tumor cells to a lymph node, L5-11, which were derived from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the differences between the primary tumor and metastases, using an isogenic heterotopic tumor transplantation model. Our data showed that the population of intratumoral MDSCs, especially polymorphonuclear MDSCs in the lymph node metastasis model were significantly increased compared with syngeneic grafts from the primary cell line Sq-1979 after 21 days. Furthermore, we identified that the lymph node metastasis cell line had increased expression of genes that promote the expansion of MDSCs, tumor growth and metastasis. Hence, these data suggest that tumor immunosuppression can occur via activation of MDSCs. However, further examination is required to clarify whether all or a subset of these factors from the lymph node metastasis tumor cells are required to induce intratumoral MDSCs.
髓源性抑制细胞（MDSCs）在炎症期间定位于造血器官和外周血，在肿瘤存在时则定位于肿瘤组织和淋巴结。然而，原发性肿瘤和转移灶中发现的MDSCs是否存在差异尚不清楚。在本研究中，我们建立了一种转移至淋巴结的肿瘤细胞系L5-11，其源自Sq-1979小鼠颊黏膜鳞状细胞癌细胞系。然后，我们使用同基因异位肿瘤移植模型分析了肿瘤免疫原性，特别是关于MDSCs的免疫原性，以阐明原发性肿瘤和转移灶之间的差异。我们的数据显示，与原发性细胞系Sq-1979的同基因移植相比，在21天后，淋巴结转移模型中肿瘤内MDSCs的数量，尤其是多形核MDSCs显著增加。此外，我们发现淋巴结转移细胞系中促进MDSCs扩增、肿瘤生长和转移的基因表达增加。因此，这些数据表明肿瘤免疫抑制可通过MDSCs的激活发生。然而，需要进一步研究以阐明淋巴结转移肿瘤细胞中的所有或部分这些因素是否是诱导肿瘤内MDSCs所必需的。
