STAT2 Mediated Epigenetic and Epitranscriptomic Regulation of CD4 ⁺ T Helper Cell Differentiation in Non-Small Cell Lung Cancer (NSCLC).

IF 5 3区医学 Q2 IMMUNOLOGY

Immunology Pub Date : 2026-06-01 Epub Date: 2026-02-04 DOI:10.1111/imm.70121

Roshni Bibi, Melvin George, Koustav Sarkar

{"title":"STAT2 Mediated Epigenetic and Epitranscriptomic Regulation of CD4 + T Helper Cell Differentiation in Non-Small Cell Lung Cancer (NSCLC).","authors":"Roshni Bibi, Melvin George, Koustav Sarkar","doi":"10.1111/imm.70121","DOIUrl":null,"url":null,"abstract":"Non-small cell lung cancer (NSCLC) is an aggressive malignancy necessitating innovative therapeutic approaches to augment antitumour immunity. Our study examined the function of the STAT2 protein in CD4+ T helper cells, which are essential for the immune response to cancer. We utilised CRISPR/Cas9 to ablate STAT2 in CD4+ T cells from stage I NSCLC patients (n = 30), assessing its impact on cellular function and diverse epigenetic pathways. Our findings indicate that the depletion of STAT2 markedly enhances the anti-cancer efficacy of T lymphocytes. Deletion of STAT2 diminished oxidative stress, enhanced the synthesis of advantageous TH1 cytokines. STAT2 depletion reduced DNA methylation and R-loop formation. T cells deficient in STAT2 showed enhanced efficacy in activating cytotoxic T lymphocytes to eliminate cancer cells. These findings identify STAT2 as a crucial regulator of immune function in the lung cancer microenvironment. Targeted STAT2 inhibition in tumour-reactive T cells may reinstate anti-tumour immunity, although systemic inhibition requires further research on targeted intervention strategies.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"293-306"},"PeriodicalIF":5.0000,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/imm.70121","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/4 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Non-small cell lung cancer (NSCLC) is an aggressive malignancy necessitating innovative therapeutic approaches to augment antitumour immunity. Our study examined the function of the STAT2 protein in CD4⁺ T helper cells, which are essential for the immune response to cancer. We utilised CRISPR/Cas9 to ablate STAT2 in CD4⁺ T cells from stage I NSCLC patients (n = 30), assessing its impact on cellular function and diverse epigenetic pathways. Our findings indicate that the depletion of STAT2 markedly enhances the anti-cancer efficacy of T lymphocytes. Deletion of STAT2 diminished oxidative stress, enhanced the synthesis of advantageous TH1 cytokines. STAT2 depletion reduced DNA methylation and R-loop formation. T cells deficient in STAT2 showed enhanced efficacy in activating cytotoxic T lymphocytes to eliminate cancer cells. These findings identify STAT2 as a crucial regulator of immune function in the lung cancer microenvironment. Targeted STAT2 inhibition in tumour-reactive T cells may reinstate anti-tumour immunity, although systemic inhibition requires further research on targeted intervention strategies.

查看原文本刊更多论文

STAT2介导的非小细胞肺癌（NSCLC）中CD4+ T辅助细胞分化的表观遗传和表转录组调控。

非小细胞肺癌（NSCLC）是一种侵袭性恶性肿瘤，需要创新的治疗方法来增强抗肿瘤免疫。我们的研究检测了STAT2蛋白在CD4+ T辅助细胞中的功能，这对癌症的免疫反应至关重要。我们利用CRISPR/Cas9去除I期NSCLC患者（n = 30） CD4+ T细胞中的STAT2，评估其对细胞功能和多种表观遗传途径的影响。我们的研究结果表明，STAT2的缺失显著增强了T淋巴细胞的抗癌功效。STAT2的缺失减少了氧化应激，增强了有利TH1细胞因子的合成。STAT2缺失减少了DNA甲基化和r -环的形成。缺乏STAT2的T细胞在激活细胞毒性T淋巴细胞消除癌细胞方面表现出增强的功效。这些发现确定STAT2在肺癌微环境中是免疫功能的关键调节因子。靶向抑制肿瘤反应性T细胞中的STAT2可能恢复抗肿瘤免疫，尽管全身性抑制需要进一步研究靶向干预策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Immunology 医学-免疫学

CiteScore

11.90

自引率

1.60%

发文量

175

审稿时长

4-8 weeks

期刊介绍： Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.