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荧光示踪鉴定放疗后淋巴结中关键的迁移树突状细胞。

Fluorescent tracking identifies key migratory dendritic cells in the lymph node after radiotherapy.

机构信息

Earle A Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.

Ronald O Perelman Department of Dermatology, Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.

出版信息

Life Sci Alliance. 2022 Apr 29;5(9). doi: 10.26508/lsa.202101337. Print 2022 Sep.

DOI:10.26508/lsa.202101337
PMID:35487695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9058260/
Abstract

Radiation therapy generates extensive cancer cell death capable of promoting tumor-specific immunity. Within the tumor, conventional dendritic cells (cDCs) are known to carry tumor-associated antigens to the draining lymph node (TdLN) where they initiate T-cell priming. How radiation influences cDC migration is poorly understood. Here, we show that immunological efficacy of radiation therapy is dependent on cDC migration in radioimmunogenic tumors. Using photoconvertible mice, we demonstrate that radiation impairs cDC migration to the TdLN in poorly radioimmunogenic tumors. Comparative transcriptional analysis revealed that cDCs in radioimmunogenic tumors express genes associated with activation of endogenous adjuvant signaling pathways when compared with poorly radioimmunogenic tumors. Moreover, an exogenous adjuvant combined with radiation increased the number of migrating cDCs in these poorly radioimmunogenic tumors. Taken together, our data demonstrate that cDC migration play a critical role in the response to radiation therapy.

摘要

放射治疗会产生大量能够促进肿瘤特异性免疫的癌细胞死亡。在肿瘤内，已知传统树突状细胞（cDC）携带肿瘤相关抗原到引流淋巴结（TdLN），在那里它们启动 T 细胞的初始激活。放射对 cDC 迁移的影响尚不清楚。在这里，我们表明放射治疗的免疫疗效取决于放射免疫原性肿瘤中 cDC 的迁移。使用光转化小鼠，我们证明放射会损害低放射免疫原性肿瘤中 cDC 向 TdLN 的迁移。比较转录分析表明，与低放射免疫原性肿瘤相比，放射免疫原性肿瘤中的 cDC 表达与内源性佐剂信号通路激活相关的基因。此外，外源性佐剂与放射相结合增加了这些低放射免疫原性肿瘤中迁移的 cDC 的数量。总之，我们的数据表明 cDC 迁移在放射治疗反应中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/9058260/13fb97b1ed3e/LSA-2021-01337_FigS11.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/9058260/2d0e0a6e0e96/LSA-2021-01337_Fig1.jpg
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