更新于：2024-05-01

CDKN1B

cyclin dependent kinase inhibitor 1B

更新于：2024-05-01

基本信息

别名

CDKN1B、cyclin dependent kinase inhibitor 1B、Cyclin-dependent kinase inhibitor 1B

+ [4]

简介

Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.

关联

100 项与 CDKN1B 相关的临床结果

登录后查看更多信息

100 项与 CDKN1B 相关的转化医学

登录后查看更多信息

0 项与 CDKN1B 相关的专利（医药）

登录后查看更多信息

5,464

项与 CDKN1B 相关的文献（医药）

2024-02-16·Scientific reports

HIF-2α-dependent TGFBI promotes ovarian cancer chemoresistance by activating PI3K/Akt pathway to inhibit apoptosis and facilitate DNA repair process.

Article

作者: Sijia Ma ; Jia Wang ; Zhiwei Cui ; Xiling Yang ; Xi Cui ; Xu Li ; Le Zhao

Hypoxia-mediated chemoresistance plays a crucial role in the development of ovarian cancer (OC). However, the roles of hypoxia-related genes (HRGs) in chemoresistance and prognosis prediction and theirs underlying mechanisms remain to be further elucidated. We intended to identify and validate classifiers of hub HRGs for chemoresistance, diagnosis, prognosis as well as immune microenvironment of OC, and to explore the function of the most crucial HRG in the development of the malignant phenotypes. The RNA expression and clinical data of HRGs were systematically evaluated in OC training group. Univariate and multivariate Cox regression analysis were applied to construct hub HRGs classifiers for prognosis and diagnosis assessment. The relationship between classifiers and chemotherapy response and underlying pathways were detected by GSEA, CellMiner and CIBERSORT algorithm, respectively. OC cells were cultured under hypoxia or transfected with HIF-1α or HIF-2α plasmids, and the transcription levels of TGFBI were assessed by quantitative PCR. TGFBI was knocked down by siRNAs in OC cells, CCK8 and in vitro migration and invasion assays were performed to examine the changes in cell proliferation, motility and metastasis. The difference in TGFBI expression was examined between cisplatin-sensitive and -resistant cells, and the effects of TGFBI interference on cell apoptosis, DNA repair and key signaling molecules of cisplatin-resistant OC cells were explored. A total of 179 candidate HRGs were extracted and enrolled into univariate and multivariate Cox regression analysis. Six hub genes (TGFBI, CDKN1B, AKAP12, GPC1, TGM2 and ANGPTL4) were selected to create a HRGs prognosis classifier and four genes (TGFBI, AKAP12, GPC1 and TGM2) were selected to construct diagnosis classifiers. The HRGs prognosis classifier could precisely distinguish OC patients into high-risk and low-risk groups and estimate their clinical outcomes. Furthermore, the high-risk group had higher percentage of Macrophages M2 and exhibited higher expression of immunecheckpoints such as PD-L2. Additionally, the diagnosis classifiers could accurately distinguish OC from normal samples. TGFBI was further verified as a specific key target and demonstrated that its high expression was closely correlated with poor prognosis and chemoresistance of OC. Hypoxia upregulated the expression level of TGFBI. The hypoxia-induced factor HIF-2α but not HIF-1α could directly bind to the promoter region of TGFBI, and facilitate its transcription level. TGFBI was upregulated in cisplatin-sensitive and resistant ovarian cancer cells in a cisplatin time-dependent manner. TGFBI interference downregulated DNA repair-related markers (p-p95/NBS1, RAD51, p-DNA-PKcs, DNA Ligase IV and Artemis), apoptosis-related marker (BCL2) and PI3K/Akt pathway-related markers (PI3K-p110 and p-Akt) in cisplatin-resistant OC cells. In summary, the HRGs prognosis risk classifier could be served as a predictor for OC prognosis and efficacy evaluation. TGFBI, upregulated by HIF-2α as an HRG, promoted OC chemoresistance through activating PI3K/Akt pathway to reduce apoptosis and enhance DNA damage repair pathway.

2024-02-07·bioRxiv : the preprint server for biology

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell.

作者: Michael A Q Martinez ; Chris Z Zhao ; Frances E Q Moore ; Callista Yee ; Wan Zhang ; Kang Shen ; Benjamin L Martin ; David Q Matus

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state, initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21 ^CIP1 /p27 ^KIP1 ) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators-including CKI-2 (p21 ^CIP1 /p27 ^KIP1 ), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (β-TrCP)-resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.

2024-02-05·Annales d'endocrinologie

Updates on the genetics of multiple endocrine neoplasia.

Review

作者: Nicolas Sahakian ; Frederic Castinetti ; Pauline Romanet ; Yves Reznik ; Thierry Brue

Multiple endocrine neoplasia (MEN) is a group of syndromes with a genetic predisposition to the appearance of endocrine tumors, and shows autosomal dominant transmission. The advent of molecular genetics has led to improvements in the management of MEN in terms of diagnosis, prognosis and therapy. The genetics of MEN is the subject of regular updates, which will be presented throughout this paper. MEN1, the first to be described, is associated with the MEN1 gene. MEN1 is well known in terms of the observed phenotype, with genetic analysis being conclusive in 90% of patients with a typical phenotype, but is negative in around 10% of families with MEN1. Improvement in analysis techniques and the identification of other genes responsable for phenocopies allows the resolution of some, but not all, cases, notably non-familial forms suspected to be fortuitous assocations with tumors. MEN4 is a rare phenocopy of MEN1 linked to constitutional mutations in the CDKN1B gene. Though it closely resembles the phenotype of MEN1, published data suggests the appearance of tumors is later and less frequent in MEN4. MEN2, which results from mutations in the RET oncogene, shows a strong genotype-phenotype correlation. This correlation is particularly evident in the major manifestation of MEN2, medullary thyroid carcinoma (MTC), in which disease aggressiveness is dependent on the pathogenic variant of RET. However, recent studies cast doubt on this correlation between MTC and pathogenic variant. Lastly, the recent description of families carrying a mutation in MAX, which is known to predispose to the development of pheochromocytoma and paraganglioma, and presents a phenotypic spectrum that evokes MEN, suggests the existence of another syndrome, MEN5.

项与 CDKN1B 相关的新闻（医药）

2024-02-15

·医药魔方Pro

中国科学家最新Nature：抗癌新靶点——FGA

原发性肝癌的致死率在全球所有癌症中高居第三，肝细胞癌（hepatocellular carcinoma, HCC）为其主要亚型，约占其所有病例的80%以上。全球每年肝癌新发病例超过一半发生在中国，且患者预后普遍较差，我国肝细胞癌患者五年总体生存率仅约为10%。肝细胞癌病因复杂，其中HCV（hepatitis C virus）感染在日本人群最为常见，酒精、非酒精性脂肪性肝炎（NASH）及代谢紊乱在西方人群中占比较大，而HBV（hepatitis B virus）慢性感染和黄曲霉毒素（aflatoxin）等致癌物暴露是中国肝癌人群的主要致病因素。既往的国际泛癌全基因组研究计划（Pan-Cancer Analysis of Whole Genomes, PCAWG）和美国癌症基因组研究计划（The Cancer Genome Atlas, TCGA）虽然包含了对肝癌全基因组特征的研究，但其样本主要为日本和西方人群，其结果不能全面反映中国人群肝癌的基因组特征。另一方面，这些研究采用了相对较浅的测序深度（~30-40X），限制了其对全基因组层面亚克隆结构的深度解析。鉴于不同区域、不同人群肝癌致病因素的巨大差异，迫切需要开展一项大规模、高深度的中国肝癌人群全基因特征分析，为开发适用于中国肝癌人群的诊断和治疗方案提供依据。来源：Nature2月14日，北京大学生物医学前沿创新中心/北京未来基因诊断高精尖创新中心白凡教授课题组联合海军军医大学王红阳院士/陈磊研究员课题组、杜克-新加坡国立大学医学院Steven G. Rozen教授课题组以及贝瑞基因吴琳博士团队合作在Nature在线发表了题为 Deep whole-genome analysis of 494 hepatocellular carcinomas的最新研究成果，完成了中国人群肝细胞癌全基因组深度特征分析（Chinese Liver Cancer Atlas, CLCA）。具体来说，该研究对494例来自中国不同地区的肝细胞癌患者肿瘤组织进行了高深度的全基因组测序（平均120x），深入分析了编码区和非编码区的驱动基因、突变印记、拷贝数变异、聚集式变异事件（clustered alteration：chromothripsis, chromoplexy和kataegis）、染色体外环状DNA（extrachromosomal circular DNA, ecDNA）以及突变演进规律等特征，揭示了以HBV相关肝细胞癌为主的全基因组变异景观，为深入理解中国人群肝细胞癌的演进机理提供了重要的线索（图1）。图1. CLCA研究方案与中国人群肝癌驱动基因全景与PCAWG-HCC队列相比，该研究的CLCA-HCC队列具有更高的HBV感染率（94.5%）、Edmondson-Steiner III-IV级分期（85.6%）和更低的HCV感染率（2.6%）、吸烟史（36.8%）及饮酒史（26.7%）占比，提示CLCA-HCC队列具有明显不同的流行病学和临床病理特征。研究首先综合多种算法，鉴定出大量新的肝癌潜在驱动事件，包括6个新编码驱动事件（FGA, HNF1A, PRDM11, CDKN1B, BMP5和ECHS1）和28个新非编码驱动事件（完整列表见原文）。值得注意的是，研究所发现的31个非编码驱动事件中仅有3个被报道过，同时多个基因都与肝脏代谢通路密切相关，该结果提示现有研究对肝癌非编码区的探究仍十分有限。通过亚克隆富集分析，研究者揭示62.5%的非编码驱动事件富集在亚克隆区域，说明非编码驱动事件并非只发生在肝癌发生早期，而是广泛参与了肝癌的亚克隆演化。其次，在PCAWG已报道的81种突变印记的基础上，本研究首次鉴定了5种新的突变印记，包括2种双碱基替换（doublet-base substitution：DBS_H1, DBS_H2）、2种插入缺失（insertion-and-deletion：ID_H3, ID_H8）和1种单碱基替换（single-base substitution signature：SBS_H8）（图2）。值得注意的是，ID_H8与黄曲霉毒素暴露相关，而DBS_H2和ID_H3则与马兜铃酸（aristolochic acid, AA）暴露相关，这些新突变印记是单碱基替换印记的重要补充。更重要的是，研究人员通过数据分析及细胞系实验共同证实SBS_H8是一种不同于马兜铃酸突变印记（SBS_22）的新型单碱基替换印记，提示其相关致病因素并非马兜铃酸。与PCAWG-HCC队列相比（0.31%），CLCA-HCC队列中SBS_H8高度富集（57.1%），并与Wnt/β-catenin信号通路的突变和预后不良密切相关。同时亚克隆富集分析揭示SBS_H8显著富集于主克隆突变中，提示该突变特征在中国人群肝细胞癌的早期演进过程中发挥重要作用。图2. 中国人群肝癌突变印记特征随后，研究还详细描绘了CLCA队列中不同类型的基因组变异事件，包括拷贝数变异、结构变异、HBV整合、ecDNA和三种类型的聚集式变异事件（Chromothripsis, chromoplexy和kataegis）（图3）。有趣的是，CLCA-HCC队列中ecDNA比例（27.3%）显著高于PCAWG-HCC队列（13.1%），同时ecDNA中整合的癌基因谱也具有独特性。虽然肝癌中HBV整合事件早有报道，但其如何整合到基因组中仍不十分清楚。该研究发现HBV可以与宿主基因组形成ecDNA，与线性DNA相比，这种HBV-oncogene-ecDNA的整合形式显著提高了临近驱动基因的拷贝数和表达水平，提示ecDNA的扩增可能在HBV相关肝癌中扮演着重要角色。Chromothripsis, chromoplexy 和kataegis等聚集式变异事件通常被认为发生在早期，也是肿瘤截断式演化（punctuated evolution）的重要证据，该研究发现这些聚集式变异事件同样存在于亚克隆事件中，提示这些基因组灾难性事件也有可能发生在肿瘤进展后期，其结果更支持肿瘤的截断-渐进双相演化模型。这一结果打破了既往对肿瘤演化规律的刻板认知，丰富了对肝癌演化模式的理解。图3. 中国人群集群突变事件特征最后，研究者还选取了三个新鉴定的潜在驱动事件（PPP1R12B, KCNJ12, FGA）进行详细功能验证，综合CRISPR定点突变及多个细胞系敲降/敲除实验，发现上述基因的突变足以导致基因表达水平的显著变化，并参与调控肝细胞癌的多种恶性表型，这些结果证实基于数据分析发现的新驱动事件的有效性。深入功能机制探究进一步揭示，潜在驱动基因FGA（编码纤维蛋白原α链，被同时鉴定为编码驱动事件和非编码驱动事件）通过负向调控TYK2-STAT3-IL6信号通路影响多种肝癌细胞的恶性表型，提示FGA及其相关信号通路有望成为肝细胞癌潜在的干预和治疗靶点（图4）。图4. FGA基因的功能机制研究总结来说，这项研究所建立的中国肝癌人群基因组变异特征全景图谱，为深入理解不同病因肝癌的发生和演进分子机制、开发全新的个体化靶向药物提供了宝贵资源，有助于提升中国肝癌的临床精准诊疗水平，造福广大肝癌患者。备注：本文转载自“北京大学生物医学前沿创新中心”，原标题：Nature | 白凡课题组与王红阳院士团队联合揭示中国人群肝癌全基因组变异及演化特征。参考资料：[1]https://www.nature.com/articles/s41586-024-07054-3推荐阅读标新生物杨小宝：突破制药边界，蛋白降解剂前景无限本导基因蔡宇伽：基因编辑疗法的“终极目标”——体内编辑圣诺医药陆阳：RNAi疗法逆势而上，实体瘤是下一个高地滨会生物刘滨磊：癌症免疫疗法下一张王牌——溶瘤病毒沙砾生物刘雅容：TIL细胞疗法突破不断，2024将是「关键年」霍德生物范靖：iPSC细胞疗法强势崛起，多种疾病治疗有望「开花结果」智核生物须涛：核药赛道火爆，2.0时代机会无限医药魔方Pro新靶点新技术新疗法商务合作：13502093012媒体合作：15895423126

2024-01-08

·GlobeNewswire-Health Care

Altamira Therapeutics to Present at 3rd Annual mRNA-Based Therapeutics Summit

HAMILTON, BERMUDA , Jan. 08, 2024 (GLOBE NEWSWIRE) -- Altamira Therapeutics to Present at 3rd Annual mRNA-Based Therapeutics Summit Altamira’s two flagship programs, AM-401 and AM-411, designed for KRAS-driven cancer and rheumatoid arthritis, serve to demonstrate the technology’s capability to enhance therapeutic efficacy HAMILTON, BERMUDA Jan. 8, 2023 (GLOBE NEWSWIRE) -- Altamira Therapeutics Ltd. ("Altamira" or the "Company") (Nasdaq: CYTO), a company providing nanoparticle-based technology for efficient RNA delivery to extrahepatic targets, announced today that it will be presenting at the 3rd Annual mRNA-Based Therapeutics Summit, being held January 23-25 at the JW Marriott Hotel, Berlin. Covadonga Pañeda, Ph.D., the Company's Chief Operating Officer, will give a presentation at the conference titled, "Delivery of therapeutic RNA in inflammation and cancer using peptide-based nanoparticles”. In addition, she will participate in the panel discussion on “Tissue specific targeting of mRNA to increase therapeutic efficacy.” "There is a strong and growing interest in the use of mRNA for highly targeted treatment of a broad range of human diseases, based on the unique ability of mRNA to promote expression of specific proteins,” Dr. Pañeda commented. “However, even the most powerful mRNA therapeutic is useless if it is not delivered safely and effectively into target cells, which has remained one of the key challenges for non-hepatic targets to date. Thanks to our SemaPhore platform we are able to deliver therapeutic mRNA, in an efficient and safe manner, to tissues harboring a tumor or suffering from acute or chronic inflammation, restricting the therapeutic effect of the drug to the site where it is needed." SemaPhore™, Altamira’s peptide-based delivery platform for mRNA, has been successfully tested so far in vivo in models of osteoarthritis (WNT16, DNMT3B), atherosclerosis (p27Kip1), aortic aneurysm (SOD2), and tumor microenvironment (ZBTB46). About Altamira Therapeutics Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a 49% stake (with additional economic rights) in its commercial-stage legacy asset Bentrio®, an OTC nasal spray for allergic rhinitis. Further, the Company is in the process of partnering / divesting its inner ear legacy assets (AM-125 nasal spray for vertigo; post Phase 2; Keyzilen® and Sonsuvi® for tinnitus and hearing loss; Phase 3). Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com Forward-Looking Statements This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Altamira’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the success of strategic transactions, including licensing or partnering, with respect to Altamira’s legacy assets, Altamira’s need for and ability to raise substantial additional funding to continue the development of its product candidates, the clinical utility of Altamira’s product candidates, the timing or likelihood of regulatory filings and approvals, Altamira’s intellectual property position and Altamira’s financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Altamira’s capital structure, including future securities offerings. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Altamira’s Annual Report on Form 20-F for the year ended December 31, 2022, and in Altamira’s other filings with the Securities Exchange Commission (“SEC”), which are available free of charge on the SEC’s website at: www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Altamira or to persons acting on behalf of Altamira are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Altamira does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law.

临床2期临床3期siRNA寡核苷酸信使RNA

2023-10-17

·药研网

认识明星小分子：IL-7

CAR-T细胞疗法的出现给许多患者带来了福音，但不可否认的是，CAR-T疗法依然存在一些普遍性问题需要解决，比如原发性和继发性耐药，效力不够等。新的研究认为，表达细胞因子介导杀伤细胞T细胞是新一代的CAR-T细胞，简单来说，就是设计表达某一细胞因子，以增强CAR-T细胞的抗肿瘤效力，提高其持久性，并改变肿瘤微环境的特征。细胞因子指的是由免疫细胞和某些非免疫细胞经刺激合成、分泌的一类具有广泛生物学活性的小分子蛋白质，具有调节免疫、生长、组织修复等多种功能。细胞因子包含白细胞介素（IL）、干扰素（IFN）、肿瘤坏死因子（TNF）、生长因子（GF）等。本期介绍一下CAR-T细胞疗法中影响T细胞功能的明星小分子 —— IL7。简介白细胞介素7（IL-7）于1987年被首次发现，1988年被正式命名为白细胞介素7，因其对体内B细胞祖细胞的生长促进作用而广受关注，是目前研究最为广泛的细胞因子之一。IL-7是一种分子量为25KDa的可溶性球状蛋白，广泛表达于骨髓、胸腺、淋巴结等淋巴器官和皮肤、肺、肝脏等非淋巴部位。作为适应性免疫系统必需的细胞因子，IL-7对B细胞发育、T细胞发育、增殖和存活至关重要。IL-7及其受体（IL-7R）的缺乏会影响B细胞、T细胞、NK细胞、单核细胞、巨噬细胞、树突状细胞和先天性淋巴细胞的发育，表明IL-7在整个免疫系统细胞发育过程中发挥着至关重要的调节作用。通路情况IL-7通过与其受体IL-7R结合，激活下游通路。IL-7R是由IL-7Rα链（又称CD127）和常见细胞因子受体γ链（又称CD132、IL-2Rγ）组成的异二聚体。值得注意的是，IL-7Rα有两种形式，分别为膜结合型和可溶性（sIL-7Rα），其中sIL-7Rα与膜IL-7Rα形成竞争关系，可以消耗过量的IL-7并拮抗IL-7信号传导，从而在细胞因子受到限制时增强IL-7的生物活性。此外sIL-7Rα可与膜表面的IL-2Rγ结合并抑制IL-2Rγ阳性细胞中的IL-7信号传导。IL-7与膜表面的IL-7Rα结合，招募IL-2Rγ形成三元信号复合物，激活下游的两个信号通路，JAK/STAT5和PI3K-AKT信号通路。IL-7信号转导通过调节细胞核内的基因表达水平来促进细胞增殖和存活并抑制细胞凋亡，包括促凋亡因子（如Bad和Bax）和细胞周期抑制剂（p21 CIP1和p27 KIP1）的减少以及抗凋亡因子（如Bcl-XL、Bcl-2、McL-1）和糖代谢调节因子（Glut1、HXKⅡ）增加。IL-7 信号通路的转导[2]IL-7在免疫和癌症中的作用IL-7 对于 B 细胞发育至关重要，因为它可以增强和维持 B 淋巴细胞生成特异性转录因子早期 B 细胞因子 1 (EBF1) 的表达，从而诱导 B 细胞产生，IL-7参与调节原 B 细胞、前 B 细胞、未成熟 B 细胞、血浆和记忆 B 细胞的产生。此外，IL-7有助于 T 细胞淋巴细胞生成和存活。当T细胞遇到抗原时，IL-7可以增强T细胞免疫反应以对抗病原体，包括拯救T细胞免于凋亡、促进幼稚T细胞分化为效应T细胞以及提高记忆T细胞的产生。除了影响B细胞和T细胞外，IL-7还在NK细胞的成熟和DC细胞的分化中起到重要作用。IL-7 在 B 细胞生命周期中的作用IL-7 在 T 细胞发育和激活中的关键作用在肿瘤中，IL-7体现出促肿瘤和抗肿瘤两种作用。IL-7通过调节免疫细胞释放IFN-γ、IL-1β、IL-1α和TNF-α等细胞因子发挥抗肿瘤作用。相反，IL-7可以通过与IL-7R结合激活JAK/STAT5、PI3K/AKT和Ras/ERK信号通路来调节Bcl-2、Bcl-xL基因表达水平，从而促进肿瘤细胞的增殖和存活。IL-7 和 IL-7R 具有促肿瘤和抗肿瘤功能[2]此外，IL-7 和 IL-7R 被认为对于调节癌症患者受损的免疫系统至关重要。IL-7 可能会减轻在癌症免疫治疗中使用 IL-2 的副作用。IL-7R介导的信号通路已广泛应用于血液瘤和一些实体瘤模型。 IL-7和IL-7R在癌症免疫治疗中的应用[2]除了在免疫和肿瘤中发挥作用外，IL-7还可以改善疫苗诱导的体液免疫反应。作为佐剂，IL-7 已被证明可以刺激抗原特异性 CD4+ T 细胞、CD8 + T 细胞和 B 细胞反应以增强疫苗效力，并增加记忆 T 和 B 细胞的产生以延长疫苗的保护作用。综上所述，IL-7有多项应用，例如制备新一代的CAR-T细胞，通过共表达IL-7延长CAR-T细胞的存活时间并提高增殖和杀伤能力；制备更优异的疫苗，提高抗肿瘤作用等。参考文献：1. https://doi.org/10.3389/fimmu.2021.7473242. https://doi.org/10.3390/ijms2318104123. https://doi.org/10.3389/fimmu.2021.680442往期推荐恒瑞医药生物药管线全梳理中生制药企业梳理石药集团生物药技术平台及管线梳理降糖减重外，GLP-1的其他作用汇总点击下方“药研网”，关注更多精彩内容

细胞疗法临床结果免疫疗法临床研究