ZymoGenetics, a Bristol-Myers Squibb Company, 1201 Eastlake Ave. East, Seattle, WA 98102, United States.
ZymoGenetics, a Bristol-Myers Squibb Company, 1201 Eastlake Ave. East, Seattle, WA 98102, United States.
Cell Immunol. 2018 Jan;323:49-58. doi: 10.1016/j.cellimm.2017.10.014. Epub 2017 Oct 31.
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells critical in mediating immune suppression in cancer patients. To develop an in vitro assay system that functionally mimics the tumor microenvironment, we cultured human monocytes with conditioned media from several cancer cell lines. Conditioned media from five tumor cell lines induced survival and differentiation of monocytes into cells characteristically similar to macrophages and MDSCs. Notably, media from the 786.O renal cell carcinoma line induced monocytes to acquire a monocytic MDSC phenotype characterized by decreased HLA-DR expression, increased nitric oxide production, enhanced proliferation, and ability to suppress autologous CD3 T cell proliferation. We further demonstrated that these in vitro MDSCs are phenotypically and functionally similar to patient-derived MDSCs. Inhibitors of STAT3, CK2, and GM-CSF resulted in partial reversal of the MDSC phenotype. MDSCs generated in vitro from 786.O tumor conditioned media represent a platform to identify potential therapeutics that inhibit MDSC activities.
髓源性抑制细胞（MDSCs）是一种未成熟的髓系细胞，在介导癌症患者的免疫抑制中起着关键作用。为了开发一种在功能上模拟肿瘤微环境的体外检测系统，我们用人单核细胞与来自几种癌细胞系的条件培养基进行培养。来自五种肿瘤细胞系的条件培养基诱导单核细胞存活并分化为具有与巨噬细胞和 MDSC 相似特征的细胞。值得注意的是，来自 786.O 肾癌细胞系的培养基诱导单核细胞获得单核细胞 MDSC 表型，其特征是 HLA-DR 表达降低、一氧化氮产生增加、增殖增强以及抑制自身 CD3 T 细胞增殖的能力增强。我们进一步证明，这些体外 MDSC 在表型和功能上与患者来源的 MDSC 相似。STAT3、CK2 和 GM-CSF 的抑制剂导致 MDSC 表型部分逆转。从 786.O 肿瘤条件培养基中体外生成的 MDSC 代表了一种识别潜在治疗药物的平台，这些药物可以抑制 MDSC 的活性。
