Impacts of neoadjuvant chemoradiotherapy on the immune landscape of esophageal squamous cell carcinoma.
Impacts of neoadjuvant chemoradiotherapy on the immune landscape of esophageal squamous cell carcinoma.
复制标题
新辅助放化疗对食管鳞癌免疫格局的影响
DOI：
10.1016/j.ebiom.2022.104371
复制
发表时间：
2022-12
期刊：
影响因子：
11.1
通讯作者：
Yang, Hong
中科院分区：
文献类型：
--
作者：
Wen, Jing;Fang, Shuogui;Hu, Yi;Xi, Mian;Weng, Zelin;Pan, Chuqing;Luo, Kongjia;Ling, Yihong;Lai, Renchun;Xie, Xiuying;Lin, Xiaodan;Lin, Ting;Chen, Jiyang;Liu, Qianwen;Fu, Jianhua;Yang, Hong
关键词：
新辅助放化疗（neoCRT）后手术是局部晚期可切除食管鳞状细胞癌（ESCC）患者最常见的方法。neoCRT如何影响ESCC肿瘤免疫微环境（TIME）尚未完全了解。进行单细胞RNA测序（scRNA-seq）以检查来自8名男性患者的8个neoCRT前和7个neoCRT后ESCC样本中的neoCRT驱动的细胞和分子动力学。获得了约112，000个细胞的scRNA-seq数据。治疗前肿瘤细胞的细胞周期、上皮发育、免疫反应和细胞外结构的表达程序与neoCRT反应有关。CD 8 + T细胞的细胞毒性和检查点分子表达之间的斯皮尔曼相关性在pre-neoCRT中间活化/耗尽的CD 8 + T细胞中是突出的。NeoCRT增加了主要和次要应答者的CD 8 + T细胞浸润，但促进了它们的耗竭。NeoCRT促进了主要应答者Th细胞的分化，但降低了Treg细胞的分化。neoCRT后cDC 1 s成熟和M2巨噬细胞标志物表达增加，而cDC 2s数量减少。neoCRT前CD 8 + T细胞和巨噬细胞中免疫相关途径的活性较高，以及neoCRT后免疫相关途径的显著减少，与neoCRT反应较好相关。neoCRT后，中间活化/耗竭的CD 8 + T细胞与巨噬细胞、cDC 1和LAMP 3 + cDC之间的相互作用减少。我们对neoCRT相关免疫变化的全面了解为ESCC对neoCRT反应相关的免疫机制提供了更深入的见解，这可能有助于未来开发改善ESCC治疗的免疫策略。本研究得到国家自然科学基金（82072607）的资助。
Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the most common approach for locally advanced resectable esophageal squamous cell carcinoma (ESCC) patients. How neoCRT impacts ESCC tumor immune microenvironment (TIME) has not been fully understood. Single-cell RNA sequencing (scRNA-seq) was conducted to examine the neoCRT-driven cellular and molecular dynamics in 8 pre- and 7 post-neoCRT ESCC samples from 8 male patients. scRNA-seq data of about 112,000 cells were obtained. Expression programs of cell cycle, epithelium development, immune response, and extracellular structure in pre-treatment tumor cells were related to neoCRT response. Spearman correlation between CD8+ T cells' cytotoxicity and expression of checkpoint molecules was prominent in pre-neoCRT intermediate activated/exhausted CD8+ T cells. NeoCRT increased CD8+ T cells’ infiltration but promoted their exhaustion in both major and minor responders. NeoCRT promoted differentiation of Th but demoted that of Treg cells in major responders. Maturation of cDC1s and expression of M2 macrophage markers increased while the number of cDC2s decreased after neoCRT. Higher activities of immune-related pathways in pre-neoCRT CD8+ T cells and macrophages, as well as a pronounced decrease of them after neoCRT, correlated with better neoCRT response. Interactions between intermediate activated/exhausted CD8+ T and macrophages, cDC1s, and LAMP3+ cDCs decreased after neoCRT. Our comprehensive picture of the neoCRT-related immune changes provides deeper insights into immunological mechanisms associated with ESCC response to neoCRT, which may aid in future development of immune-strategies for improving ESCC treatment. This work was supported by the National Natural Science Foundation of China (82072607).
登录
查看更多内容
影响因子：
3.8
作者：
Lee, Dong U.;Katavolos, Paula;Danilenko, Dimitry M.
通讯作者：
Danilenko, Dimitry M.
表观遗传药物筛选发现 IOX1 通过靶向 TET2 为 Th17 介导的炎症抑制剂
影响因子：
11.1
作者：
Hu, Xiao;Zou, Yanli;Copland, David A.;Schewitz-Bowers, Lauren P.;Li, Yan;Lait, Philippa J. P.;Stimpson, Madeleine;Zhang, Zhihui;Guo, Shixin;Liang, Juanran;Chen, Tingting;Li, Jing Jing;Yuan, Sujing;Li, Shuo;Zhou, Penghui;Liu, Yizhi;Dick, Andrew D.;Wen, Xiaofeng;Lee, Richard W. J.;Wei, Lai
通讯作者：
Wei, Lai
Bromodomain 和末端外蛋白抑制剂 OTX015 抑制 T 辅助细胞增殖和分化
影响因子：
2.5
作者：
Hu, Xiao;Schewitz-Bowers, Lauren P.;Wei, Lai
通讯作者：
Wei, Lai
影响因子：
6
作者：
Dutta A;Venkataganesh H;Love PE
通讯作者：
Love PE