Cytotoxic T cell immunity against the non-immunogenic, murine, hepatocellular carcinoma Hepa1-6 is directed towards the novel alternative form of macrophage colony stimulating factor

• Published in: Cellular immunology 2009, Vol.259 (2), p.117-127
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Alt-macrophage colony stimulating factor; Animals; Antigens, Neoplasm - immunology; Autoimmunity; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cytotoxic T lymphocytes; Cytotoxicity Tests, Immunologic; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Hepa1-6; Hepatocellular carcinoma; HepG2; Humans; Immunization; Immunohistochemistry; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - immunology; Liver Neoplasms, Experimental - prevention & control; Macrophage colony stimulating factor; Macrophage Colony-Stimulating Factor - administration & dosage; Macrophage Colony-Stimulating Factor - biosynthesis; Macrophage Colony-Stimulating Factor - genetics; Macrophage Colony-Stimulating Factor - immunology; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RMA-S; RNA - chemistry; RNA - genetics; T-Lymphocytes, Cytotoxic - immunology; Transduction, Genetic; Tumor immunity
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2009.06.008

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.