ARID1A Deficiency Regulates Anti-Tumor Immune Response in Esophageal Adenocarcinoma.
ARID1A Deficiency Regulates Anti-Tumor Immune Response in Esophageal Adenocarcinoma.
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ARID1A缺陷调节食管腺癌的抗肿瘤免疫应答
DOI：
10.3390/cancers15225377
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发表时间：
2023-11-12
期刊：
影响因子：
5.2
通讯作者：
Bhowmick, Neil A.
中科院分区：
文献类型：
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作者：
Zhang, Le;Zheng, Yueyuan;Chien, Wenwen;Ziman, Benjamin;Billet, Sandrine;Koeffler, H. Phillip;Lin, De-Chen;Bhowmick, Neil A.
已知 9-15% 的食管腺癌 (EAC) 肿瘤存在 ARID1A 突变。研究表明ARID1A突变在肿瘤免疫表型中发挥作用。我们的目的是研究 ARID1A 缺陷对 EAC 的免疫调节作用。我们的研究表明 ARID1A 在免疫反应和脂质代谢途径的调节中发挥作用。我们的研究结果还为 ARID1A 在 EAC 中的功能作用及其对涉及免疫检查点阻断疗法的未来临床测试的潜在影响提供了宝贵的见解。 ARID1A 被鉴定为免疫检查点阻断疗法的潜在生物标志物可能有助于选择更有可能从这种治疗方法中受益的患者。 ARID1A 是染色质重塑 SWI/SNF 复合体的成员，在许多癌症类型中经常丢失，包括食管腺癌 (EAC)。在这里，我们研究 ARID1A 缺陷对 EAC 抗肿瘤免疫反应的影响。我们发现具有 ARID1A 突变的 EAC 肿瘤与肿瘤浸润 CD8+ T 细胞水平增强相关。 ARID1A 缺陷的 EAC 细胞表现出增强的 IFN 反应信号，并促进 CD8+ T 细胞募集和细胞溶解活性。此外，我们证明 ARID1A 调节 EAC 中的脂肪酸代谢基因，表明脂肪酸代谢还可以调节 EAC 细胞中 CD8+ T 细胞的募集和 CD8+ T 细胞的细胞溶解活性。这些结果表明 ARID1A 缺陷影响 EAC 中的肿瘤免疫和脂质代谢，对 EAC 中的免疫检查点阻断治疗具有重要意义。
It is known that 9–15% of esophageal adenocarcinoma (EAC) tumors have ARID1A mutations. Studies have shown that ARID1A mutations play a role in the tumor immune phenotype. We aimed to investigate the immunomodulating effects of ARID1A deficiency in EAC. Our study implicates that ARID1A plays a role in the regulation of both the immune response and lipid metabolism pathways. Our findings also provide valuable insights into the functional role of ARID1A in EAC and its potential implications for future clinical testing involving immune checkpoint blockade therapy. The identification of ARID1A as a potential biomarker for immune checkpoint blockade therapy may help in selecting patients who are more likely to benefit from this treatment approach. 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.
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DOI：
10.4291/wjgp.v5.i4.534
发表时间：
2014-11-15
期刊：
World journal of gastrointestinal pathophysiology
影响因子：
--
作者：
Alexandre, Leo;Long, Elizabeth;Beales, Ian Lp
通讯作者：
Beales, Ian Lp
影响因子：
5.2
作者：
通讯作者：
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影响因子：
24.5
作者：
Quante, Michael;Wang, Timothy C.;Bass, Adam J.
通讯作者：
Bass, Adam J.
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
影响因子：
6
作者：
通讯作者：
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