GILT in tumor cells improves T cell-mediated anti-tumor immune surveillance
GILT in tumor cells improves T cell-mediated anti-tumor immune surveillance
复制标题
肿瘤细胞中的 GILT 改善了 T 细胞介导的抗肿瘤免疫监视。
DOI：
10.1016/j.imlet.2021.04.001
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发表时间：
2021-04-12
影响因子：
4.4
通讯作者：
Yang, Jie
中科院分区：
文献类型：
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作者：
Li, Hongshuai;Wang, Yuan;Yang, Jie
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，肿瘤细胞中的GILT表达是否与T细胞介导的抗肿瘤反应的改善有关仍不清楚。在这里，我们确定GILT是能够促进抗肿瘤免疫监视通过促进MHC I类介导的抗原呈递在结肠癌。通过使用荷结肠癌小鼠模型，我们发现GILT抑制肿瘤生长在体内，更多的白细胞浸润，但没有影响肿瘤细胞的增殖，细胞周期和迁移在体外的发展。此外，通过使用转基因OT-I小鼠，我们识别了肿瘤表达的OVA肽，一种替代肿瘤抗原，我们发现GILT能够增强MHCI类介导的抗原呈递，并提高特异性CD 8（+）T细胞抗肿瘤反应。这些发现提出了肿瘤中GILT-MHC-I轴的增强作为免疫系统对抗癌症的可行选择。
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.