髓源性抑制细胞对乳腺癌细胞“干性”获得的生物学和力学特性调控及其分子机制研究

Myeloid derived suppressor cells(MDSCs) play a key role in the war between the tumor and the host. They inhibit the anti-tumor ability of the host and induce tumor immune escape which STAT3 passway is involved in. The latest report showed that MDSCs could facilitate the acquisition of cancer stem cells (CSCs) phenotype. The tumor microenvironment factors can promote the expression of programmed cell death ligand1 (PDL1) in tumor cells, which is involved in the occurrence and development of tumor cell immune escape, and to be associated with the activation of STAT3.However, how the MDSCs regulate the generation of cancer stem cells is unclear. In this study, we mainly intend to explore the effect of MDSCs and PDL1 on CSCs. We sort MDSCs and breast cancer cells from MMTV-Esp1 C57BL/6 mice. The MDSCs and cancer cells are co-cultured in three-dimensional type-Ⅰcollagen gels or in plate which are used to investigate the mammarysphere formation and CSCs proportion. To explore the influence of MDSCs and PDL1 on CSCs in vivo, CSCs were.transplanted in NOD/SCID mice. We discuss the role of MDSCs and PDL1 in the regulatory effect on breast cancer cells‘ dynamic properties by using matrix embedded beads and 3D motility assay. What we do will provide mechanistic explanation for tumor immunotherapy.

髓源性抑制细胞(Myeloid derived suppressor cells, MDSCs)在肿瘤和宿主博弈过程中扮演重要角色。该群细胞促使肿瘤发生免疫逃逸，近来研究还发现MDSCs有促使癌细胞获得“干性”的功能。此外，肿瘤微环境炎症因子可促进肿瘤细胞高表达PDL1,后者也参与肿瘤细胞的免疫逃逸及发生发展。本课题拟研究MDSCs和程序性死亡配体1（Programmed cell death ligand1, PDL1）之间的联系及对乳腺癌细胞“干性”获得和力学特性的影响。构建并培养PDL1不同表达水平的乳腺癌细胞系，检测MDSCs及PDL1的表达和对CSCs形成及其成瘤能力的影响，探究内在机制，并用记录性聚焦显微镜和3D细胞追踪程序分析MDSCs对乳腺癌干细胞力学特性和侵袭能力的影响。这将为乳腺癌的免疫治疗提供新思路。