title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Ge
authors.forename: Jian Gang
authors.initials: JG
authors.lastname: Zhang
authors.forename: Christina A
authors.initials: CA
authors.lastname: Samathanam
authors.forename: Christina
authors.initials: C
authors.lastname: Delgado
authors.forename: Mary
authors.initials: M
authors.lastname: Tarbiyat-Boldaji
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Dan
authors.forename: Neil
authors.initials: N
authors.lastname: Hoa
authors.forename: Tuong-Vi
authors.initials: TV
authors.lastname: Nguyen
authors.forename: Reza
authors.initials: R
authors.lastname: Alipanah
authors.forename: Jimmy T H
authors.initials: JT
authors.lastname: Pham
authors.forename: Ramon
authors.initials: R
authors.lastname: Sanchez
authors.forename: H Terry
authors.initials: HT
authors.lastname: Wepsic
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jadus
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: D000951:Antigens, Neoplasm; D020033:Protein Isoforms; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor