CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.
Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.
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T细胞通过组织和淋巴器官再循环,以扫描其同源抗原。放射治疗提供位点特异性的细胞毒性以杀死癌细胞,但也有可能消除照射野内的肿瘤特异性T细胞。为了动态研究放射对CD8 T细胞再循环的影响,我们使用Kaede小鼠模型对肿瘤浸润细胞进行光转换,并监测它们移出放射野的过程。我们证明放射导致CD8 T细胞从肿瘤向淋巴结及远处部位的再循环丧失。使用scRNASeq,我们观察到放射治疗后肿瘤中增殖的CD8 T细胞减少,导致耗竭表型比例性富集。相比之下,放射后5天,T细胞从肿瘤向肿瘤引流淋巴结的再循环增加,与对治疗肿瘤的免疫监视增强相对应。这些数据表明,肿瘤放射治疗暂时损害了从治疗部位到引流淋巴结及远处未治疗肿瘤的系统性T细胞再循环。这可能为优化时机治疗以改善系统性T细胞介导的肿瘤免疫提供依据。
T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation.
We demonstrate that radiation results in loss of CD8 T cell recirculation from the tumor to the lymph node and to distant sites. Using scRNASeq, we see decreased proliferating CD8 T cells in the tumor following radiation therapy resulting in a proportional enrichment in exhausted phenotypes.
By contrast, 5 days following radiation increased recirculation of T cells from the tumor to the tumor draining lymph node corresponds with increased immunosurveillance of the treated tumor. These data demonstrate that tumor radiation therapy transiently impairs systemic T cell recirculation from the treatment site to the draining lymph node and distant untreated tumors. This may inform timing therapies to improve systemic T cell-mediated tumor immunity.
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