Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, The People's Republic of China.
Cancer Immunol Immunother. 2010 Feb;59(2):313-21. doi: 10.1007/s00262-009-0752-1.
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.
MHC-I 抗原表面表达的减少或丢失部分归因于 MHC-I 抗原加工机制的各种成分的失调。越来越多的证据表明，自噬除了在维持细胞内稳态方面起着至关重要的作用外，在 MHC-II 表面表达中也起着重要作用。在这里，我们报告自噬是 B16 黑色素瘤细胞中 MHC-I 抗原表达的负调节剂；然而，在 IFN-γ 的存在下，它被转化为正调节剂。我们表明，自噬不仅参与 MHC-I 抗原的降解，而且还参与 MHC-I 结合肽的产生。对于这两个过程，IFN-γ 干扰 MHC-I 抗原的降解，而不是影响肽的产生。使用 B16 黑色素瘤小鼠模型，我们进一步表明自噬可能在黑色素瘤的早期增强 CTL 对黑色素瘤细胞的细胞溶解作用，但在晚期损害细胞溶解作用。这种不同的结果可能是由于肿瘤进展过程中 IFN-γ 的水平不同。总之，我们的研究结果表明，自噬参与 MHC-I 抗原表达的调节，通过这种调节，自噬可以在肿瘤免疫中发挥不同的作用。
