Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
Induction of immunity to a viral protein that had been transfected into a tumor cell line was studied. The nucleoprotein (NP) of vesicular stomatitis virus (VSV) was used as a model tumor-associated Ag after transfection into EL-4, and H-2b thymoma originating from C57BL/6 mice. The NP-transfected cell line (EL-4NP) was lysed by NP-specific CTL and was found to restimulate NP-specific CTL in vitro as efficiently as did VSV-infected macrophages. Despite both of these in vitro characteristics, C57BL/6 mice inoculated with EL-4NP did not mount a measurable NP-specific CTL response and developed a lethal tumor as rapidly as did mice given control EL-4. This lack of immunogenicity could not be explained by down-regulation of MHC class I molecules or by loss of NP; even EL-4NP cells metastasizing to the spleen kept their high restimulatory capacity and excellent target characteristics. However, once mice were immunized with VSV or with a vaccinia-VSV-NP recombinant virus they were protected against tumor growth of EL-4NP by CD8+ CTL but not by CD4+ T cells. Taken together, the failure of the tumor-associated Ag to induce a protective T cell response in vivo despite its excellent capacity to restimulate CTL in vitro may encourage adjuvant immunotherapy in cancer; even the effects of weakly immunizing tumor vaccines, e.g., recombinant viruses, may be efficiently amplified by tumor cells.
Kündig
T M
TM
Institute of Experimental Immunology, University of Zürich, Switzerland.
Bachmann
M F
MF
Lefrancois
L
L
Puddington
L
L
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013945:Thymoma; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*; D014779:Virus Replication
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D016827:CD8 Antigens; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014758:Viral Core Proteins