Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China.
Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China.
Immunol Lett. 2021 Jun;234:1-12. doi: 10.1016/j.imlet.2021.04.001. Epub 2021 Apr 7.
The lysosomal thiol reductase GILT catalyzes the reduction of disulfide bonds of protein antigens, facilitating antigen-presenting cells (APCs) to present antigen to T cells. However, whether GILT expression in tumor cells can be associated with improved T cell-mediated anti-tumor responses remains unknown. Here, we identify that GILT is able to facilitate anti-tumor immune surveillance via promoting MHC class I mediated-antigen presentation in colon carcinoma. By using mice model bearing colon tumors, we find that GILT inhibites tumor growth in vivo with more leucocytes infiltration but has no effect on tumor cell development in vitro in terms of proliferation, cell cycle and migration. Furthermore, by using transgenic OT-I mice, we recognize the tumor-expressing OVA peptide, a surrogate tumor antigen, we find that GILT is capable of enhancing MHC class I mediated antigen presentation and improving specific CD8 T cell anti-tumor responses in murine colon carcinoma. These findings propose the boost of GILT-MHC-I axis in tumors as a viable option for immune system against cancer.
溶酶体巯基还原酶 GILT 催化蛋白质抗原的二硫键还原,促进抗原呈递细胞 (APC) 将抗原呈递给 T 细胞。然而,肿瘤细胞中 GILT 的表达是否与改善 T 细胞介导的抗肿瘤反应有关尚不清楚。在这里,我们确定 GILT 能够通过促进 MHC Ⅰ类介导的抗原呈递来促进结肠癌的抗肿瘤免疫监视。通过使用携带结肠肿瘤的小鼠模型,我们发现 GILT 在体内抑制肿瘤生长,体内浸润的白细胞增多,但在体外对肿瘤细胞的增殖、细胞周期和迁移没有影响。此外,通过使用转基因 OT-I 小鼠,我们识别到肿瘤表达的 OVA 肽,一种替代肿瘤抗原,我们发现 GILT 能够增强 MHC Ⅰ类介导的抗原呈递,并改善小鼠结肠癌中特异性 CD8 T 细胞的抗肿瘤反应。这些发现提出了在肿瘤中增强 GILT-MHC-I 轴作为免疫系统对抗癌症的一种可行选择。