Ge Lisheng, Zhang Jian Gang, Samathanam Christina A, Delgado Christina, Tarbiyat-Boldaji Mary, Dan Qinghong, Hoa Neil, Nguyen Tuong-Vi, Alipanah Reza, Pham Jimmy T H, Sanchez Ramon, Wepsic H Terry, Morgan Timothy R, Jadus Martin R
Pathology and Laboratory Medicine Service, Diagnostic and Molecular Medicine Health Care Group, VA Long Beach Healthcare System, 5901 E. 7th Street, Long Beach, CA 90822, USA.
Cell Immunol. 2009;259(2):117-27. doi: 10.1016/j.cellimm.2009.06.008. Epub 2009 Jun 23.
Mouse Hepa1-6 hepatocellular carcinoma (HCC) cells were transduced with the membrane form of macrophage colony stimulating factor (mM-CSF). When mM-CSF transduced Hepa1-6 cells were injected subcutaneously into mice, these cells did not form tumors. The spleens of these immunized mice contained cytotoxic CD8+ T lymphocytes (CTL) that killed the unmodified Hepa1-6 cells. We show that the alternative form of macrophage colony stimulating factor (altM-CSF) induced CTL-mediated immunity against Hepa1-6 cells. AltM-CSF is restricted to the H-2D(b) allele. CTLs killed RMA-S cells loaded with exogenous altM-CSF peptide. Vaccination of mice with dendritic cells pulsed with the altM-CSF peptide stimulated anti-Hepa1-6 CTLs. Hyper-immunization of mice with mM-CSF Hepa1-6 cells showed inflammation of the liver and kidneys. Although altM-CSF was expressed within liver and kidney cells, its intensity was lower than Hepa1-6 cells. AltM-CSF was detected within the human HepG2 cell line. These studies suggest that altM-CSF may be a tumor antigen for HCC.
用巨噬细胞集落刺激因子的膜形式（mM-CSF）转导小鼠Hepa1-6肝癌（HCC）细胞。当将转导了mM-CSF的Hepa1-6细胞皮下注射到小鼠体内时，这些细胞未形成肿瘤。这些免疫小鼠的脾脏中含有可杀死未修饰的Hepa1-6细胞的细胞毒性CD8 + T淋巴细胞（CTL）。我们发现巨噬细胞集落刺激因子的替代形式（altM-CSF）可诱导针对Hepa1-6细胞的CTL介导的免疫。AltM-CSF受限于H-2D(b)等位基因。CTL杀死了负载有外源性altM-CSF肽的RMA-S细胞。用altM-CSF肽脉冲处理的树突状细胞对小鼠进行疫苗接种可刺激抗Hepa1-6 CTL。用mM-CSF Hepa1-6细胞对小鼠进行超免疫显示肝脏和肾脏出现炎症。尽管altM-CSF在肝细胞和肾细胞中表达，但其强度低于Hepa1-6细胞。在人HepG2细胞系中检测到了altM-CSF。这些研究表明，altM-CSF可能是肝癌的肿瘤抗原。
