Defective presentation of endogenous antigens by a murine sarcoma. Implications for the failure of an anti-tumor immune response.
MHC class I-restricted CTL play a central role in the immune response against methylcholanthrene (MCA)-induced sarcomas in mice. We, therefore, hypothesized that MCA-induced tumors may evade immune recognition by failing to present Ag to CD8+ CTL. Of a number of previously described MCA-induced sarcomas, one, MCA 101, fails to induce CTL, is nonimmunogenic, and grows rapidly and lethally in nonimmunosuppressed recipients. To better understand the nonimmunogenicity of MCA 101 we examined its ability to present foreign Ag to CTL. Unlike immunogenic sarcomas, MCA 101 failed to present endogenously synthesized influenza virus Ag to influenza virus-specific CTL. The deficiency in presentation of endogenous Ag by MCA 101 was attributed to a markedly reduced rate of synthesis of class I molecules because up-regulation of class I synthesis by IFN-gamma greatly increased the presentation of influenza A virus Ag. Despite low levels of cell surface class I expression, MCA 101 presented exogenous peptide Ag to anti-influenza CTL with efficiency similar to immunogenic MCA sarcoma cell lines. These findings could not be attributed to deficiencies in class I assembly or transport, as has been suggested by others who have studied mutant cells with defective Ag presentation. Furthermore, our studies suggest that some tumor cells can escape recognition by CTL and subsequent immune eradication by suppressing presentation of endogenous Ag.
Restifo
N P
NP
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Esquivel
F
F
Asher
A L
AL
Stötter
H
H
Barth
R J
RJ
Bennink
J R
JR
Mulé
J J
JJ
Yewdell
J W
JW
Rosenberg
S A
SA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000956:Antigens, Viral / Q000032:analysis; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma