Spranger Stefani, Dai Daisy, Horton Brendan, Gajewski Thomas F
Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA.
Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA; Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA.
Cancer Cell. 2017 May 8;31(5):711-723.e4. doi: 10.1016/j.ccell.2017.04.003.
Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103 dendritic cells (DCs) in T cell-inflamed tumors. Our data indicate that lack of CD103 DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape.
效应T细胞具有识别和杀死癌细胞的能力。然而，肿瘤是否能够通过将效应T细胞排除在肿瘤微环境之外而产生免疫抗性尚不清楚。通过使用一种类似于非T细胞炎症性人类肿瘤的肿瘤模型，我们评估了过继性T细胞转移是否可以克服自发启动失败的问题。流式细胞术检测结合活体成像表明效应T细胞向肿瘤内的转运失败。从机制上讲，这是由于缺乏CXCL9/10，我们发现CXCL9/10是由T细胞炎症性肿瘤中的CD103树突状细胞（DCs）产生的。我们的数据表明，肿瘤微环境中缺乏CD103 DCs主要抵抗抗肿瘤T细胞反应的效应阶段，从而导致免疫逃逸。
