更新于：2024-11-01

TBX21

更新于：2024-11-01

基本信息

别名

T-bet、T-box protein 21、T-box transcription factor 21

+ [6]

简介

Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs (PubMed:10761931). Activates transcription of a set of genes important for Th1 cell function, including those encoding IFN-gamma and the chemokine receptor CXCR3. Induces permissive chromatin accessibilty and CpG methylation in IFNG (PubMed:33296702). Activates IFNG and CXCR3 genes in part by recruiting chromatin remodeling complexes including KDM6B, a SMARCA4-containing SWI/SNF-complex, and an H3K4me2-methyltransferase complex to their promoters and all of these complexes serve to establish a more permissive chromatin state conducive with transcriptional activation (By similarity). Can activate Th1 genes also via recruitment of Mediator complex and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1) in the form of the super elongation complex (SEC) to super-enhancers and associated genes in activated Th1 cells (PubMed:27292648). Inhibits the Th17 cell lineage commitment by blocking RUNX1-mediated transactivation of Th17 cell-specific transcriptinal regulator RORC. Inhibits the Th2 cell lineage commitment by suppressing the production of Th2 cytokines, such as IL-4, IL-5, and IL- 13, via repression of transcriptional regulators GATA3 and NFATC2. Protects Th1 cells from amplifying aberrant type-I IFN response in an IFN-gamma abundant microenvironment by acting as a repressor of type-I IFN transcription factors and type-I IFN-stimulated genes. Acts as a regulator of antiviral B-cell responses; controls chronic viral infection by promoting the antiviral antibody IgG2a isotype switching and via regulation of a broad antiviral gene expression program (By similarity). Required for the correct development of natural killer (NK) and mucosal-associated invariant T (MAIT) cells (PubMed:33296702).

关联

项与 TBX21 相关的药物

SB-020

靶点

TBX21

作用机制

TBX21 modulators

在研机构-

原研机构

sterna biologicals GmbH

在研适应症-

非在研适应症

银屑病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

SB-021

靶点

TBX21

作用机制

TBX21 modulators

在研机构-

原研机构

sterna biologicals GmbH

在研适应症-

非在研适应症

慢性阻塞性肺疾病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TBX21 相关的临床结果

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100 项与 TBX21 相关的转化医学

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0 项与 TBX21 相关的专利（医药）

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4,415

项与 TBX21 相关的文献（医药）

2025-12-01·Journal of Clinical Immunology

Investigation of Transcription Factor and Cytokine Gene Expression Levels in Helper T Cell Subsets Among Turkish Patients Diagnosed with ICF2 (Novel ZBTB24 gene Variant) and ICF3 (CDCA7 Variant) Syndrome

Article

作者: Kuccukturk, Serkan ; Gul, Yahya ; Reisli, Ismail ; Guner, Sukru Nail ; Karaselek, Mehmet Ali ; Sahin, Ali ; Duran, Tugce ; Keles, Sevgi

Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF), is a rare disease with autosomal recessive inheritance. ICF syndrome. It has been reported that ICF syndrome is caused by mutations in the DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) genes. As a result of literature research, there are no studies on transcription factor and cytokine expressions of helper T cell subsets in ICF syndrome. In the study; Th1 (TBET, STAT1, STAT4), Th2 (GATA3, STAT6), Th17 (RORgt, STAT3), Treg (FoxP3, STAT5) transcription factors and the major cytokines of these cells (Th1; IFNG, Th2; IL4, Th17; IL17A-21-22, Treg; IL10, TGFβ) expressions were aimed to be evaluated by qRT-PCR. Patients (ICF3: three patients; ICF2: two patients), six heterozygous individual and five healthy controls were included in the study. All patients had hypogammaglobulinemia. Except for the CD19 cells of P2 from patients diagnosed with ICF3, the CD3, CD4, CD8, and CD19 cells in the other ICF3 patients were normal. However, the rates of these cells were low in patients with ICF2 syndrome. Factors belonging to patients' Th1, Th17 and Treg cells were significantly lower than the control. Additionally, novel mutation was detected in ZBTB24 gene (c.1121-2 A > T). Our study is the first molecular study on Th cell subsets in patients with ICF syndrome and a new mutation that causes ICF2 syndrome has been identified.

2025-01-01·Journal of Ethnopharmacology

Qingchang suppository ameliorates mucosal inflammation in ulcerative colitis by inhibiting the differentiation and effector functions of Th1 and Th17 cells

Article

作者: Liu, Huosheng ; Lin, Jiang ; Cao, Hui ; Dai, Xiaoling ; Shan, Jingyi ; Yuan, Jianye ; Shi, Bei

ETHNOPHARMACOLOGICAL RELEVANCEQing Chang Suppository (QCS), a traditional Chinese medicine formula, has been shown to effectively alleviate mucosal inflammation in patients with ulcerative colitis (UC). While the mechanism of QCS appears to be related to the regulation of CD4⁺T cell subset responses, direct evidence demonstrating that QCS inhibits Th1 and Th17 cell activation in UC (particularly based on human data) remains lacking. Additionally, the precise mechanisms through which QCS affects these cells have yet to be fully elucidated.AIM OF STUDYThis study aimed to investigate the effects of QCS on Th1 and Th17 cell responses in UC and to explore the underlying mechanisms.MATERIALS AND METHODSTwenty-eight patients with mild-to-moderate UC were recruited and treated with QCS for 12 weeks. Symptoms were assessed every two weeks, with sigmoidoscopies performed at baseline and at week 12. Intestinal mucosal biopsies and peripheral blood (PB) were collected at these time points. At the end of the trial, patients were categorized into responder and non-responder groups based on a modified Mayo disease activity index score. Healthy controls (HCs) were defined as subjects without IBD or colorectal carcinoma but with colon polyps. The frequencies of IFN-γ⁺CD4⁺T cells and IL-17A⁺CD4⁺T cells in PB and colonic mucosa were measured using flow cytometry. The expression levels and localization of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A were determined via immunofluorescence, and JNK signaling activation was assessed through immunoblotting and immunohistochemistry. All parameters were compared across the three groups.RESULTSAt week 12, responders showed a significant reduction in colonic mucosal inflammation compared to baseline, accompanied by decreased frequencies of IFN-γ⁺CD4⁺T and IL-17A⁺CD4⁺ T cells in both PB and the colonic epithelial layer. Notably, Th1 and Th17 cell activity around intestinal epithelial cells (IECs) was nearly undetectable, as evidenced by the diminished expression of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A. Additionally, JNK phosphorylation in these cells was significantly reduced. In contrast, non-responders exhibited no meaningful improvement; colonic pathology remained unchanged, and elevated levels of IFN-γ⁺CD4⁺T and IL-17A⁺CD 4⁺T cells persisted in both the PB and colonic epithelial layer. The presence of Th1 and Th17 cells and their associated cytokines around IECs remained substantial, and there was no significant change in JNK activation.CONCLUSIONQCS attenuates mucosal inflammation in UC patients by inhibiting the differentiation and effector functions of Th1 and Th17 cells, primarily through the regulation of the JNK signaling pathway.

2025-01-01·Journal of Ethnopharmacology

The protective effects and mechanisms of essential oil from Chimonanthus nitens Oliv. leaves in allergic rhinitis based on the NF-κB and T-bet/GATA-3 signaling pathways

Article

作者: Huang, Xiaoying ; Liang, Xinli ; Dong, Wei ; Qian, Xingyi ; Liu, Duanyong ; Gao, Beibei ; Yang, Ming ; Zuo, Zhengyun

ETHNOPHARMACOLOGICAL RELEVANCEPreliminary studies showed that Shanlameiye granules are derived from Chimonanthus nitens Oliv. Leaves ameliorate inflammatory responses in mice with Allergic Rhinitis (AR). The essential oil from Chimonanthus nitens Oliv. Leaves (CLO) have been identified as the key active substances in these granules. However, whether CLO constitutes the primary mechanism for the mitigation of AR-related inflammation by these granules has not yet been investigated.AIM OF THE STUDYThis experiment was to validate the effects and mechanism of CLO on inflammatory responses in RAW264.7 cells and AR rat model.MATERIALS AND METHODSAn inflammatory model was induced in RAW264.7 cells by Lipopolysaccharide (LPS) & Interferon-gamma (IFN-γ) stimulation. AR rat model was established using both systemic and local challenges with Ovalbumin (OVA).RESULTSIn cell experiments, CLO obviously decreased the secretion of cytokines and inhibited the NF-κB signaling pathway activation. In animal experiments, CLO decreased the number of eosinophils in the blood and lowered the levels of cytokines in nasal lavage fluid (NALF). Additionally, CLO inhibited the expression of STAT6, GATA-3, and p-p65, while increasing the expression of STAT4 and T-bet in the nasal mucosa.CONCLUSIONIn AR rat model, CLO may play an anti-inflammatory role in AR rat model by regulating NF-κB and T-bet/GATA-3 signaling pathways.

项与 TBX21 相关的新闻（医药）

2024-10-24

·奇点网

关键少数决定整体命运，这恒河里

*仅供医学专业人士阅读参考虽然CD8+T细胞毫无疑问是抗肿瘤免疫应答的主导者，但看过这么多研究的大家想必也都明白，它们“能不能C”往往要看其它各方面给不给面子，像是CD4+T细胞当中的调节性T细胞（Tregs）就经常去当免疫抑制的反派角色，搞得奇点糕对CD4+T细胞整体的印象都不好了，但其实CD4+T细胞里面也是有好兄弟的，甚至有可能作用举足轻重呢。比如今天，美国埃默里大学研究者们在《自然》上发表的研究成果就显示，肿瘤引流淋巴结（TDLNs）内存在一种具有干细胞样特征，可自我更新和继续分化的CD4+T细胞（特征为PD1+TCF+lin-），它们的分化命运会直接决定CD8+T细胞能否真正成为效应T细胞，进而控制肿瘤微环境内抗肿瘤免疫应答的走向。这类PD1+TCF+CD4+T细胞虽然原本可以向效应T细胞等不同方向分化，但在同为CD4+T细胞的Tregs约束下，它们分化产生的基本只能是Tregs；只有当Tregs被专门清除时，PD1+TCF+CD4+T细胞才能被“松绑”，分化为1型辅助性T细胞（Th1 Cells），并通过产生IFN-γ来帮CD8+T细胞分化为效应表型，要助力免疫治疗当然也要朝这个方向发力引导了。一图总结论文核心内容埃默里大学研究团队的第一步工作，是以肾癌为分析对象，用单细胞RNA测序和流式细胞术分析来阐明CD4+T细胞的异质性，但分析所见却相当有意思：肿瘤微环境和TDLNs内浸润的CD4+T细胞当中，除了大家熟悉的Tregs和Th1细胞外，还有多达65%其实是“沉默的大多数”，就像完全置身事外的旁观者。具体来说，这些CD4+T细胞会高表达PD-1，也会表达提示干细胞样特征的TCF-1和一些共刺激分子，但不表达任何主要的谱系定义转录因子（lineage-defining transcription factors, 即BCL6, TBX21, GATA3或RORC，下文简称为lin-），增殖能力和辅助性评分相对最低，也不会表达各种效应分子和抑制性受体，整体处在类似休眠的状态。肿瘤和TDLNs中的大多数CD4+T细胞其实是“沉默的旁观者”然而“沉默的大多数”既然存在，就不会一点意义都没有。研究者们将PD1+TCF+lin-CD4+T细胞（由于CD4+T细胞普遍高表达PD-1，以下简写为TCF+lin-CD4+T细胞）分离出来，在体外条件下用不同的细胞因子处理或施加抗原刺激，发现它们仍具备向CD4+效应T细胞、Tregs和Th1细胞等不同方向分化和快速增殖的能力，即有着明确的干细胞样特征，且分化后克隆扩增的T细胞受体（TCR）克隆型也与肿瘤内的CD4+效应T细胞吻合，这说明TCF+lin-CD4+T细胞就是CD4+效应T细胞的前体细胞。接下来在荷瘤小鼠上的实验显示，植入肿瘤的第1周，大多数CD4+T细胞就在TDLNs内转化为了TCF+lin-表型，但肿瘤微环境内占主导地位的却是Tregs，TCF+lin-CD4+T细胞变成了少数派。在体外条件下能好好分化，到了肿瘤微环境内就只能变成Tregs，说明TCF+lin-CD4+T细胞的分化命运，受到了肿瘤微环境内另外一些“无形大手”的操控。通过PD-L1抑制剂处理排除PD-1/L1通路的影响后，研究者们就把嫌疑人锁定为了Tregs，将它们清除果然改写了TCF+lin-CD4+T细胞的分化命运：肿瘤和TDLNs内的CD4+T细胞数量不仅显著扩增，表型也变为以Th1细胞为主，TCR克隆型显示它们确实由TCF+lin-CD4+T细胞分化而来，抗肿瘤免疫应答也同时比之前强多了。Tregs会操控TCF+lin-CD4+T细胞分化命运，进而决定抗肿瘤免疫应答进一步分析显示，TCF+lin-CD4+T细胞是否能挣脱Tregs的束缚，向Th1细胞分化，也直接决定了TDLNs内CD8+T细胞能否分化为效应表型，而CD8+T细胞其实也有点“沉默的大多数”特征，它们同样具有干细胞样特征，但必须接收到Th1细胞产生的IFN-γ信号，才会上调各种效应分子表达并发生数量扩增，然后斗志昂扬进入肿瘤微环境去干掉癌细胞。由TCF+lin-CD4+T细胞分化而来的Th1细胞产生的IFN-γ，是让CD8+T细胞进入效应表型的关键最后研究者们证实，约有15%的人类肾癌患者是CD4+T细胞层面的“幸运儿”，即TCF+lin-CD4+T细胞能向Th1细胞分化（标志为转录因子TBET阳性），这部分患者接受免疫治疗后的生存预后更好。所以说，调动“沉默的大多数”确实有举足轻重的意义，把原本啥事儿不干的CD4+T细胞激活起来，不就相当于天降了一支抗癌生力军？而且同样的道理，好像下个月在大洋彼岸还挺有适用性的参考文献：Cardenas M A, Prokhnevska N, Sobierajska E, et al. Differentiation fate of a stem-like CD4 T cell controls immunity to cancer[J]. Nature, 2024.本文作者丨谭硕

免疫疗法

2024-10-03

·佰傲谷BioValley

免疫衰老关键细胞

细胞是机体的基本组成单位，其发生衰老会导致低能量效应、并驱动整体衰老，免疫细胞是衰老细胞的关键调节因子，其在衰老过程中也出现功能失调。 doi: 10.1038/s41392-023-01502-8. 造血干细胞（HSC） HSC衰老是免疫衰老的基础。衰老HSC会分化为各类功能失调的免疫细胞，导致免疫衰老。衰老HSC的主要特征是自我更新、分化偏向、能量代谢改变。HSC衰老特点细胞分化偏向更偏向形成骨髓细胞，淋巴细胞减少，导致骨髓-淋巴失衡。诱导偏向的细胞因子： IL-1/3/6； TNFα； IFN； G-CSF、M-CSF、GM-CSF。能量代谢改变从无氧糖酵解转向氧化磷酸化。由此产生ROS引起氧化应激，导致DNA损伤、细胞凋亡。自我更新减弱细胞周期活性降低。中性粒细胞年龄相关疾病与中性粒细胞功能降低相关，而中性粒细胞发育、数量的改变不大。中性粒细胞衰老特点功能降低吞噬能力降低；粘附性、趋化性异常；细胞凋亡增加； NET释放异常； TLR功能异常。中性粒细胞表达CXCR2可以响应CXCL1向炎症部位迁移，但衰老的中性粒细胞CXCR2表达下调，导致其迁移功能异常，不仅使抗炎作用降低，同时会引起非炎症部位损伤。单核/巨噬巨噬细胞功能恶化是免疫衰老的一个关键因素，其清除组织中衰老细胞的能力会随年龄增加而减弱，表现自噬水平降低、抵抗病毒感染的能力缺陷。巨噬细胞衰老特点SASP表型 IL-1β、IL-6、TNFα产生增加； IL-10产生减少，导致更易纤维化。代谢改变糖酵解、线粒体OXPHOS降低，导致能量不足，细胞功能受损。细胞周期异常细胞周期检查点p16INK4a、p21CIP1表达上调。 NK细胞随年龄增长，外周血和骨髓中NK祖细胞数量未受影响，而NK总数增加，不过NK细胞增殖、杀伤能力下降。NK细胞衰老特点细胞比例改变 CD56（bright）NK减少（未成熟）； CD56（dim）NK增加（成熟）。NK激活受损NK激活受体NKp30、NKp46、DNAM1表达降低，免疫监视功能受损。细胞毒性减弱穿孔素、颗粒酶、IFNα、IFNγ产生减少； IL-1/4/6/8/10、TNFα产生增加。 B细胞生命周期中B细胞生成会持续进行，但虽年龄增长因骨髓生态位变化导致B细胞输出受影响。B细胞衰老特点比例改变骨髓前体B细胞、浆细胞减少；外周抗体反应性记忆B细胞减少，耗竭记忆B细胞增加。促炎记忆B细胞产生促炎细胞因子： IL-1α、IL-1β、IL-6、TNFα。 B细胞与年龄相关的改变也是疫苗接种后抗体反应下降的主要原因。60~75岁人群接种流感疫苗的血清阳性保护率也仅为41~58%，75岁以上人群更低为29~46%。同时B细胞多样性崩溃，各类自身抗体产生增加。 T细胞正常情况下，T细胞数量靠胸腺输出和外周幼稚T细胞增殖来维持，而随年龄增长T细胞数量失衡；而且衰老与T细胞间的关系非常微妙，衰老会引起T细胞功能障碍，功能失调的T细胞又会释放多种炎症分子加速衰老。T细胞衰老特点数量改变Treg数量增加。 Th数量增加，其中CD4幼稚T细胞PU.1、BATF、IRF4转录因子网络诱导Th9分化偏好。 CD8循环初始T细胞数量减少； CD8效应T细胞增加，BATF、IRF4促进初始T细胞向效应T细胞转化，并上调效应功能相关转录因子（T-bet、Runx3、Blimp-1）。效应功能减弱炎症水平升高Treg虽然数量增加，但抑制能力减弱，间接诱导炎症。 Th1、Th2分泌细胞因子能力减弱，免疫防御功能下降； Th9通过产生IL-9参与自身免疫性和各类炎症性疾病过程。记忆T细胞CD27、CD28共刺激分子丢失，出现耗竭表型； CD45RA+CD8+T细胞出现SASP表型，产生高水平IL-18、ADAM28，促进炎症。小结随着机体衰老，大多免疫细胞表现出衰老特征，内在表现为衰老/受损细胞清除效率降低，外在表现为免疫抵抗力减弱。而且由细胞的衰老相关分泌表型（SASP）所引起的慢性炎症不仅是衰老的结果，也是促进衰老进一步发展的重要原因，由此上升到器官、组织，最终会导致各类疾病发生。 doi: 10.1038/s41392-023-01502-8. 参考资料 Li X et al. Inflammation and aging: signaling pathways and intervention therapies. Signal Transduct Target Ther. 2023;8(1):239. Published 2023 Jun 8. doi: 10.1038/s41392-023-01502-8. Yousefzadeh MJ et al. An aged immune system drives senescence and ageing of solid organs. Nature. 2021 Jun;594(7861):100-105. Mogilenko DA, Shpynov O, Andhey PS, et al. Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging. Immunity. 2021;54(1):99-115.e12. Hagen M, Derudder E. Inflammation and the Alteration of B-Cell Physiology in Aging. Gerontology. 2020;66(2):105-113. 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

临床研究疫苗临床结果

2024-09-24

·奇点网

又促癌又利好免疫治疗，墙头草啊这是

*仅供医学专业人士阅读参考看多了人体内各种细胞争先恐后给癌细胞当帮凶的研究，奇点糕总有种误入了某全员内鬼酒厂，啊不组织的感觉，哪天真跳出来个助力抗癌的“正面人物”，奇点糕都得看着论文标题愣一下才敢相信，这叫什么个事儿啊。不过奇点糕的这种刻板印象其实也不算错，今天要介绍的助力癌症免疫治疗的“正面人物”也确实不是细胞，而是肠道微生物的一员。近日，香港中文大学医学院于君领衔的研究团队在Cancer Cell期刊发表了最新研究成果[1]，首次揭示常在结直肠癌（CRC）中富集、且可能导致CRC发生发展的具核梭杆菌（Fusobacterium nucleatum），竟然还会助力免疫治疗激活CD8+T细胞，从而使免疫治疗在此前疗效不佳的微卫星稳定型（MSS）CRC中打开突破口，真是意想不到啊。研究发现，具核梭杆菌可产生大量丁酸，抑制CD8+T细胞中的组蛋白去乙酰化酶（HDAC）3/8，由此诱导Tbx21基因启动子的H3K27乙酰化和表达上调，作为转录调节因子的TBX21就能转录抑制CD8+T细胞表达PD-1，从而缓解CD8+T细胞耗竭，恢复它们的效应功能，因此MSS型CRC患者瘤内的具核梭杆菌丰度较高，也与免疫治疗效果较好相关。一图总结论文核心内容MSS型CRC占全部CRC的85%以上，奇点糕都记不清免疫治疗在这里多少次碰得头破血流了，所以能发现具核梭杆菌这个“自己人”内应，确实挺出乎意料的.特别是此前还有研究显示，在免疫治疗已取得突破的微卫星不稳定型（MSI）CRC中，具核梭杆菌丰度可能与CD8+T细胞的浸润呈负相关；但在MSS型CRC中，相关性又掉转成了正相关[2]。于君团队就从这项结论看似有些矛盾性的研究出发，开始探究具核梭杆菌对MSS型CRC的免疫治疗到底有什么影响。对25例患者的初步分析显示，肿瘤组织样本内的具核梭杆菌丰度，与患者接受免疫治疗的生存预后（PFS/OS）呈正相关，乃至与免疫治疗是否对CRC肝转移有效都有关；将瘤内富集具核梭杆菌CRC患者的粪菌移植到荷瘤小鼠体内，也可显著改善小鼠对免疫治疗的应答，且肿瘤内的CD8+T细胞显著增多、耗竭细胞占比则减少。具核梭杆菌丰度可预测MSS型CRC对免疫治疗的应答研究者们又采用先以抗生素处理清除小鼠肠道菌群、再饲喂具核梭杆菌的方法证实，具核梭杆菌确实会加速MSS型CRC在小鼠体内的增殖，与既往研究发现一致，但瘤内存在具核梭杆菌也会使荷瘤小鼠对PD-1抑制剂治疗的应答更好，且瘤内浸润的主要是具有较强细胞毒效应功能的CD8+T细胞（IFN-γ+/TNF-α+/GZMB+），而非耗竭CD8+T细胞（PD-1+）。具核梭杆菌是如何激活CD8+T细胞主导的免疫应答，就是接下来要明确的问题了，研究者们认为奥秘可能与具核梭杆菌的某种分泌物质有关，并在实验中证实具核梭杆菌的条件培养液（CM）就足以增敏PD-1抑制剂治疗，而且还能直接作用于CD8+T细胞；研究者们又按分泌物分子质量进行了分层分析，证实关键物质的分子量<3 kDa。而在37种分子量符合<3 kDa条件的候选物质中，富集程度受具核梭杆菌存在与否影响最大的就是丁酸，用它单独处理CD8+T细胞就能起到改善细胞毒效应功能、缓解耗竭状态的作用，并在细胞/类器官/小鼠实验中都对免疫应答有正向激活作用，下一步研究的主要对象当然就是它啦。丁酸是具核梭杆菌外分泌影响CD8+T细胞状态和功能的关键物质通过单细胞RNA测序，研究者们发现具核梭杆菌CM处理或丁酸直接处理，都会上调CD8+T细胞的Tbx21基因表达，它编码的TBX21是对CD8+T细胞激活有关键作用的细胞因子；接下来的实验则揭示，具核梭杆菌外分泌丁酸调控Tbx21基因表达的机制，是经典的表观遗传套路启动子H3K27乙酰化，丁酸会通过抑制HDAC3/8的功能来推动这个进程，从而促进TBX21表达上调，以此不让CD8+T细胞表达PD-1，这样就能保住CD8+T细胞的抗癌积极性了。具核梭杆菌外分泌的丁酸，主要通过表观遗传机制上调Tbx21表达，下调CD8+T细胞的PD-1表达所以说，看似对免疫治疗极为抗拒的MSS型CRC里，其实也有免疫治疗可以利用的机会，至少瘤内具核梭杆菌丰度就有可能成为临床可用的Biomarker。不过，直接补充丁酸这招可能不灵，因为丁酸正常情况下在体内的半衰期只有6分钟，而具核梭杆菌是在瘤内产生丁酸，投递距离太近了才能避开这个问题，基于具核梭杆菌设计治疗策略或许才是正解。------奇点糕近期推出了《2024ASCO年会深度盘点》课程，为大家系统盘点了2024ASCO年会上实体瘤领域的重磅进展，让您在100分钟内迅速深入把握前沿。长按识别下图中的二维码即可购买，购买后您可以在「奇点网小程序」收听，或下载奇点网「医学奇点」苹果客户端收听。如果遇到任何技术问题，大家可以戳我们下图中的客服小伙伴来解决~~参考文献：[1]Wang X, Fang Y, Liang W, et al. Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer[J]. Cancer Cell, 2024.[2]Hamada T, Zhang X, Mima K, et al. Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status[J]. Cancer Immunology Research, 2018, 6(11): 1327-1336.本文作者丨谭硕

免疫疗法临床研究微生物疗法