Immunosuppressive Myeloid-Derived Suppressor Cells Can Be Converted into Immunogenic APCs with the Help of Activated NKT Cells: An Alternative Cell-Based Antitumor Vaccine
Immunosuppressive Myeloid-Derived Suppressor Cells Can Be Converted into Immunogenic APCs with the Help of Activated NKT Cells: An Alternative Cell-Based Antitumor Vaccine
复制标题
DOI：
10.4049/jimmunol.0802430
复制
发表时间：
2009-02-15
影响因子：
4.4
通讯作者：
Kang, Chang-Yuil
中科院分区：
文献类型：
--
作者：
Ko, Hyun-Jeong;Lee, Jung-Mi;Kang, Chang-Yuil
骨髓来源的抑制细胞（MDSC），这是已知的，积累在血液，脾脏，和骨髓中的荷瘤小鼠和癌症患者，被测试为APC的细胞疫苗，因为它们具有表型相似性与炎症单核细胞，并可能从相同的前体分化为单核细胞。尽管MDSC具有免疫抑制特性，但体内转移的MDSC（其呈递肿瘤抗原和NKT细胞配体（α-半乳糖神经酰胺））以CD 8（+）细胞、NK细胞和NKT细胞依赖性方式与CD 4（+）T细胞和宿主树突状细胞非依赖性方式显著延长了转移性荷瘤小鼠的生存时间。在疫苗中使用MDSC作为APC的主要问题是它们对CTL的抑制和对Foxp 3（+）调节性T细胞的诱导。然而，α-半乳糖神经酰胺负载的MDSC不抑制CD 4（+）和CD 8（+）T细胞，并允许产生Ag特异性CTL免疫，而不增加调节性T细胞的产生。此外，用活化的NKT细胞刺激诱导MDSC的表型或成熟标志物的变化，包括CD 11b、CD 11 c和CD 86。总之，这些发现表明NKT细胞促进免疫抑制性MDSC转化为免疫原性APC，引发成功的抗肿瘤免疫，并为替代的基于细胞的疫苗提供基础。免疫学杂志，2009，182：1818-1828.
Myeloid-derived suppressor cells (MDSCs), which are known to be accumulated in the blood, spleen, and bone marrow of tumor-bearing mice and cancer patients, were tested as APCs for a cellular vaccine because they have phenotypical similarity with inflammatory monocytes and may be differentiated from the same precursors as monocytes. Although MDSCs have immunosuppressive properties, in vivo transferred MDSCs, which present tumor Ag and NKT cell ligand (alpha-galactosylceramide), significantly prolonged survival time in metastatic tumor-bearing mice in a CD8(+) cell-, NK cell-, and NKT cell-dependent manner vs a CD4(+) T cell- and host dendritic cell-independent manner. Major concerns about using MDSCs as APCs in a vaccine are their suppression of CTLs and their induction of Foxp3(+) regulatory T cells. However, alpha-galactosylceramide-loaded MDSCs did not suppress CD4(+) and CD8(+) T cells and allowed for the generation of Ag-specific CTL immunity without increasing the generation of regulatory T cells. Furthermore, stimulation with activated NKT cells induced changes on MDSCs in phenotypical or maturation markers, including CD11b, CD11c, and CD86. Taken together, these findings suggest that NKT cells facilitate the conversion of immunosuppressive MDSCs into immunogenic APCs, eliciting successful antitumor immunity and providing the basis for alternative cell-based vaccines. The Journal of Immunology, 2009, 182: 1818-1828.