Autophagy facilitates major histocompatibility complex class I expression induced by IFN-γ in B16 melanoma cells.
The reduction or loss of MHC-I antigen surface expression in human and murine tumor cells is partly attributable to the dysregulation of various components of the MHC-I antigen-processing machinery. Accumulating evidence suggests that autophagy, besides its vital role in maintaining the cellular homeostasis, plays an important role in MHC-II surface expression. Here, we report that autophagy is a negative regulator of MHC-I antigen expression in B16 melanoma cells; however, in the presence of IFN-γ, it is converted to a positive regulator. We show that autophagy not only participates in the degradation of MHC-I antigen but also plays a role in the generation of MHC-I-binding peptides. For these two processes, IFN-γ interferes with MHC-I antigen degradation, rather than affecting peptide generation. Using B16 melanoma mouse model, we further show that autophagy may enhance the cytolysis of CTL to melanoma cells at the early stage of melanoma, but impairs the cytolysis at the late stage. Such different consequences may be explained by the different levels of IFN-γ during tumor progression. Taken together, our findings demonstrate that autophagy is involved in the regulation of MHC-I antigen expression, through which autophagy can play different roles in tumor immunity.
Li
Bo
B
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, The People's Republic of China.
Lei
Zhang
Z
Lichty
Brain D
BD
Li
Dong
D
Zhang
Gui-Mei
GM
Feng
Zuo-Hua
ZH
Wan
Yonghong
Y
Huang
Bo
B
D000818:Animals; D001343:Autophagy; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D012878:Skin Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma
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