文章：

ARID1A缺失调控食管腺癌抗肿瘤免疫应答机制研究

ARID1A Deficiency Regulates Anti-Tumor Immune Response in Esophageal Adenocarcinoma

原文发布日期：12 November 2023

DOI: 10.3390/cancers15225377

类型: Article

开放获取: 是

英文摘要：

ARID1A, a member of the chromatin remodeling SWI/SNF complex, is frequently lost in many cancer types, including esophageal adenocarcinoma (EAC). Here, we study the impact of ARID1A deficiency on the anti-tumor immune response in EAC. We find that EAC tumors with ARID1A mutations are associated with enhanced tumor-infiltrating CD8+T cell levels. ARID1A-deficient EAC cells exhibit heightened IFN response signaling and promote CD8+T cell recruitment and cytolytic activity. Moreover, we demonstrate that ARID1A regulates fatty acid metabolism genes in EAC, showing that fatty acid metabolism could also regulate CD8+T cell recruitment and CD8+T cell cytolytic activity in EAC cells. These results suggest that ARID1A deficiency shapes both tumor immunity and lipid metabolism in EAC, with significant implications for immune checkpoint blockade therapy in EAC.

摘要翻译： 

ARID1A作为染色质重塑复合体SWI/SNF的组成亚基，在包括食管腺癌在内的多种癌症类型中频繁缺失。本研究旨在探讨ARID1A缺失对食管腺癌抗肿瘤免疫应答的影响。研究发现，携带ARID1A突变的食管腺癌组织中肿瘤浸润性CD8+T细胞水平显著升高。ARID1A缺陷的食管腺癌细胞表现出增强的干扰素应答信号传导，并能促进CD8+T细胞的募集及其细胞毒活性。进一步研究表明，ARID1A通过调控食管腺癌中的脂肪酸代谢相关基因，影响CD8+T细胞的募集与细胞毒活性。这些发现揭示ARID1A缺失同时重塑食管腺癌的肿瘤免疫与脂质代谢特征，对食管腺癌免疫检查点阻断治疗策略具有重要启示。

原文链接：

ARID1A Deficiency Regulates Anti-Tumor Immune Response in Esophageal Adenocarcinoma