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.
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.
Ge
Lisheng
L
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.
Zhang
Jian Gang
JG
Samathanam
Christina A
CA
Delgado
Christina
C
Tarbiyat-Boldaji
Mary
M
Dan
Qinghong
Q
Hoa
Neil
N
Nguyen
Tuong-Vi
TV
Alipanah
Reza
R
Pham
Jimmy T H
JT
Sanchez
Ramon
R
Wepsic
H Terry
HT
Morgan
Timothy R
TR
Jadus
Martin R
MR
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
D000951:Antigens, Neoplasm; D020033:Protein Isoforms; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor