中文摘要
肿瘤如何教育巨噬细胞成为M2型,以及如何靶向M2型巨噬细胞是当前肿瘤免疫研究的重点。肿瘤细胞死亡释放大量微颗粒(细胞膜包裹细胞内容物形成的囊泡结构)到肿瘤微环境中。微颗粒包含肿瘤细胞的信息,巨噬细胞是否会因吞噬肿瘤微颗粒而受到肿瘤的教育?我们先前实验证实,巨噬细胞有效摄取肿瘤微颗粒并呈现M2表型。我们前期工作还证实,肿瘤微颗粒能够包裹化疗药物,其被肿瘤细胞摄取后将肿瘤细胞杀伤。进一步研究,我们发现肿瘤微颗粒亦能够作为载体,靶向溶瘤病毒至肿瘤细胞,诱导肿瘤细胞死亡。基于课题组前期工作,本项目拟以肿瘤微颗粒为切入点,探究肿瘤相关M2型巨噬细胞生成的共有内在机理,同时采用肿瘤微颗粒包裹化疗药物或溶癌病毒的策略,探究药物杀伤或利用病毒的刺激信号再教育肿瘤相关巨噬细胞的新途径。本项目的实施,有望在肿瘤相关巨噬细胞这一关键性肿瘤研究领域取得原创、突破性进展,为肿瘤免疫治疗提供新思路。
英文摘要
Elucidation of the mechanism underlying tumor education of macrophages and development strategies to target tumor-associated macrophages is critical in tumor immunology. Tumor cell death results in the release of abundant microparticles (vesicular structure formed by cellular membrane packaging cytoplasmic contents) into tumor microenvironment. Phagocytosis is a prototypal function of macrophages. Whether macrophages are educated to M2 type after taking up tumor-microparticles remains unclear. Our previous studies showed that macrophages effectively took up tumor cell-derived microparticles and subsequently expressed M2 phenotype, and tumor-microparticles acted as vectors to deliver chemotherapeutic drugs or oncolytic viruses to tumor cells. Based on these data, in the present study, we try to explore whether tumor-microparticles function as a common pathway through which macrophages are educated to M2 type and address the underlying mechanism. Moreover, we in turn use these microparticles to deliver chemo-drugs or oncolytic viruses to macrophage and cytolyze tumor-associated macrophages or re-educate them based on the stimulatory signals of viruses. All in all, this study might result in original progression on tumor-associated macrophages so to provide new potential strategy in tumor immunotherapy.
