التفاصيل البيبلوغرافية
| العنوان: |
Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma. |
| المؤلفون: |
Zhou, Yong, Mo, Shanlan, Cui, Heyang, Sun, Ruifang, Zhang, Weimin, Zhuang, Xiaofei, Xu, Enwei, Li, Hongyi, Cheng, Yikun, Meng, Yongsheng, Liu, Meilin, Yan, Ting, Liu, Huijuan, Zhang, Ling, Yang, Bin, Xi, Yanfeng, Wang, Shubin, Cheng, Xiaolong, Li, ShuaiCheng, Liu, Zhihua |
| المصدر: |
National Science Review; May2024, Vol. 11 Issue 5, p1-16, 16p |
| مصطلحات موضوعية: |
SQUAMOUS cell carcinoma, SOMATIC mutation, TUMOR suppressor genes, TUMOR microenvironment, T cells |
| مستخلص: |
Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2 , accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the esophagus. Interestingly, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+ T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy. Collectively, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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