TSHR

NEW YORK, Oct. 29, 2024 (GLOBE NEWSWIRE) -- Immunovant, Inc. (Nasdaq: IMVT), a clinical-stage immunology company dedicated to enabling normal lives for people with autoimmune diseases, today announced that data from the Phase 2a trial of batoclimab in Graves’ disease will be the subject of an oral presentation of a late-breaking abstract accepted for the 2024 American Thyroid Association (ATA) Annual Meeting being held October 30 to November 3, 2024, in Chicago, Illinois. New data highlighting both thyroid-specific and extrathyroidal manifestations of Graves' disease will be presented. Late-Breaking Oral Presentation Details: Title:Efficacy and Safety of the FcRn Inhibitor, Batoclimab, in Graves’ Thyroidal and Extrathyroidal Disease: a Proof-of-concept StudyPresentation:#0020Session:#5 – Autoimmune Thyroid DiseaseDate and Time:Friday, November 1, 2024, 4:05pm – 5:05pm ETPresenter:George Kahaly, MD, PhD About Graves’ disease Graves’ disease is an autoimmune disorder associated with the overproduction of thyroid hormones and is the most common cause of hyperthyroidism. Although Graves’ disease can affect any age group or gender, it occurs often in women younger than 40 years of age. In Graves’ disease, harmful IgG autoantibodies bind to and activate the thyroid-stimulating hormone receptor present on the thyroid gland, stimulating excess thyroid hormone production. Existing treatments, which include antithyroid drugs, radioactive iodine, and thyroid surgery, are aimed at reducing thyroid hormone levels to lessen the severity of symptoms. These treatments have remained largely unchanged for the past 70 years. About Immunovant, Inc. Immunovant, Inc. is a clinical-stage immunology company dedicated to enabling normal lives for people with autoimmune diseases. As a trailblazer in anti-FcRn technology, the Company is developing innovative, targeted therapies to meet the complex and variable needs of people with autoimmune diseases. For additional information on the Company, please visit immunovant.com. Contact:Renee Barnett, MBA Chief Financial Officer Immunovant, Inc. info@immunovant.com Source: Immunovant, Inc.

Septerna just entered the clinic, and its lack of human data makes it an outlier among the companies able to successfully go public this year in what is still a cautious biotech IPO market. What the young company does have is technology based on research from a Nobel laureate and a lead drug candidate that could offer a key advantage over other treatments for a rare, inherited disease. Now it has $288 million in IPO cash to support its pipeline. Late Thursday, Septerna priced its offering of 16 million shares at $18 apiece, going beyond the preliminary financial terms it previously set. Those shares will trade on the Nasdaq under the stock symbol “SEPN.” South San Francisco-based Septerna will use most of the IPO proceeds to continue clinical testing of SEP-786 for hypoparathyroidism, an inherited deficiency of parathyroid hormone (PTH). This hormone regulates calcium and phosphate levels in the blood. Lacking this hormone leads to fatigue, brain fog, and muscle weakness. In more severe cases, patients can develop cardiovascular problems and renal failure. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Standard hypoparathyroidism treatment includes calcium and vitamin D supplements, which do not address all of the disease’s symptoms. Takeda Pharmaceutical’s Natpara, an engineered version of parathyroid hormone, will cease production by the end of the year due to manufacturing issues. In August, the FDA approved Ascendis Pharma’s Yorvipath, the first in what could be wave of new injectable peptide hypoparathyroidism drugs. Septerna takes a different approach to the disease with SEP-786, a small molecule that targets and activates the parathyroid hormone 1 receptor (PTH1R), sparking it to produce more of the key hormone. As an oral drug, SEP-786 would offer patients less burdensome dosing. “Hormone replacement with injectable PTH peptides, either marketed or in clinical development, may improve blood chemistry profiles of patients via PTH1R activation but will require lifelong daily injections,” Septerna said in the IPO filing. “We believe there is a substantial opportunity for an oral small molecule therapy that offers convenience, improved compliance, and potentially superior efficacy.” PTH1R is a G protein coupled-receptor (GPCR), part of a family of receptors that regulate a wide range of physiological processes. The role of these receptors in both health and disease is known, and many of them are targeted by FDA-approved drugs. However, an estimated 75% of GPCR targets remain undrugged, Septerna said in the filing. Septerna’s platform technology enables scientists to isolate a GPCR and study it outside of a cell, but in a way that replicates what happens to that receptor inside a cell. With this greater understanding of GPCRs, the company designs, screens for, and optimizes small molecules that target the receptors. This technology platform, called Native Complex, is based on the research of Robert Lefkowitz, a Duke University professor of biochemistry and chemistry who was awarded the 2012 Nobel Prize in Chemistry for his work in the GPCR field. In animal tests, Septerna reported its small molecule agonists activated PTH1R and regulated key genes important for calcium homeostasis in manner similar to native parathyroid hormone. A placebo-controlled Phase 1 study will evaluate the safety and tolerability of once-daily and twice-daily dosing of the SEP-786 in healthy volunteers. The first patient was dosed last month. Preliminary data are expected in mid-2025. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President The Septerna pipeline includes two preclinical negative allosteric modulators. SEP-631 is in development for immunology and inflammation indications, such as the skin disease chronic spontaneous urticaria. TSHR has potential applications in endocrinology. Native Complex has also yielded small molecule agonists of the GLP-1, GIP, and glucagon receptors for the potential treatment of metabolic disorders. An oral Septerna drug that hits one or more of these receptors could put the biotech in competition with commercialized injectable peptide drugs, such as Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy. But Septerna will likely aim to stand out from the next wave of metabolic medications in development as pills. This competition includes Structure Therapeutics, whose small molecules come from its own GPCR platform technology (when Structure went public last year, it snagged the fitting stock symbol “GPCR”). Lead Structure drug candidate GSBR-1290 is currently in mid-stage clinical development for type 2 diabetes and obesity. Since Septerna’s inception in 2019, the company had raised $224.2 million prior to the IPO, most recently a $150 million Series B round last year led by RA Capital Management. That firm holds a 7.7% post-IPO stake in Septerna, according to the prospectus. Third Rock Ventures is Septerna’s largest shareholder with a 23.6% post-IPO stake. Septerna is led by CEO Jeff Finer, who is also a venture partner at Third Rock. Septerna’s plans resonated with investors, whose interest in the biotech’s stock enabled the company to boost the IPO size twice. In preliminary financial terms set at the beginning of the week, Septerna planned to offer more than 10.9 million shares in the range of $15 to $17 each, which would have raised $175 million at the pricing midpoint. On Thursday, the biotech boosted the deal size to more than 15.2 million shares priced at $18 apiece, which would have raised $275 million at the pricing midpoint. Late Thursday, the biotech again revised the terms upward, boosting the deal to $288 million. As of the end of the second quarter of this year, Septerna reported its cash position was $155.7 million. Following the IPO, the company plans to spend $54 million to advance lead drug candidate SEP-786 through Phase 2 testing in hypoparathyroidism, according to the filing. The company also plans to use the capital to develop additional molecules that target the parathyroid hormone receptor. Another $24 million will support the completion of Phase 1 testing of SEP-631 and additional molecule inhibitors that could be potential treatments for chronic spontaneous urticaria. And $41 million is set aside for other R&D, including Septerna’s TSHR and incretin receptor programs.

OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769 文章来源：外泌体之家 9月份国内新出的细胞外囊泡/外泌体领域论文不完全统计有390篇。IF>10的有92篇；IF>20的有12篇。本期主要内容包括：癌症相关恶病质、成骨作用、胆固醇在外泌体递释RNA药物中的关键作用、纳米封装的肿瘤囊泡用作自体肿瘤疫苗、胃癌转移、增强非小细胞肺癌的免疫治疗、免疫检查点抑制剂相关的心脏毒性、肝细胞癌中T细胞介导的抗肿瘤免疫、结直肠癌免疫逃逸、血友病关节软骨缺损的整体修复、抑制血管钙化和衰老、肺部疫苗接种、肾缺血再灌注损伤和纤维化、糖尿病伤口治疗、衰老和年龄相关功能障碍、水凝胶微针贴片促进慢性伤口愈合、工程益生菌递送双纳米抗体、动脉粥样硬化等方面内容。内容十分丰富，不容错过。外泌体之家 1.北京大学詹启敏、王嫣：GRP75触发白色脂肪组织褐变，促进癌症相关恶病质 Chen, X., et al. (2024). "GRP75 triggers white adipose tissue browning to promote cancer-associated cachexia."  Signal Transduct Target Ther 9(1): 253. IF=40.8 恶病质影响50%-80%的癌症患者，是一种使人虚弱的综合征，导致20%的癌症相关死亡。恶病质的一个关键特征是脂肪组织萎缩，但其如何促成恶病质的发展却知之甚少。该研究在癌症恶病质小鼠模型中证明，白色脂肪组织褐变可能是一种早期发病特征，它发生在体重减轻和骨骼肌萎缩之前。通过分析来自恶病质诱导肿瘤的细胞外囊泡中差异表达的蛋白质，确定了一种分子伴侣——葡萄糖调节蛋白75（GRP75），作为脂肪细胞褐变的关键介质。从机制上讲，GRP75与腺嘌呤核苷酸转位酶2（ANT2）结合形成GRP75-ANT2复合物。稳定的ANT2增强了其与解偶联蛋白1的相互作用，导致后者表达升高，进而促进脂肪细胞褐变。用GRP75抑制剂醉茄素治疗可以逆转这种褐变，并在体内减轻恶病质表型。该研究结果揭示了肿瘤衍生的GRP75在恶病质发展过程中调节白色脂肪组织褐变的一种新机制，并提出了一种以白色脂肪组织为中心的早期恶病质干预潜在靶向方法。 2.解放军总医院唐佩福团队：组蛋白去乙酰化酶抑制可增强来自肌肉的细胞外囊泡，通过miR-873-3p促进成骨作用 Chen, M., et al. (2024). "Histone deacetylase inhibition enhances extracellular vesicles from muscle to promote osteogenesis via miR-873-3p."  Signal Transduct Target Ther 9(1): 256. 有规律的身体活动被广泛认为可以降低各种疾病的风险，其中骨骼肌通过释放对多个器官和组织有益的生物分子发挥关键作用。然而，许多人，特别是老年人和患有某些临床病症的人，无法进行体育锻炼，这就需要采取替代策略来刺激肌肉细胞分泌有益的生物分子。组蛋白乙酰化和去乙酰化对运动诱导的基因表达有显著影响，这表明靶向组蛋白去乙酰化酶（HDACs）可以模拟一些运动反应。这项研究探讨了HDAC抑制剂曲古抑菌素A（TSA）对人骨骼肌成肌细胞（HSMMs）的影响。研究结果表明，TSA诱导的高乙酰化增强了肌管融合，并增加了富含miR-873-3p的细胞外囊泡（EVs）的分泌。这些TSA-EVs通过靶向H2调宁蛋白（CNN2）促进了人骨髓间充质干细胞（hBMSCs）的成骨分化。在体内，对骨质疏松小鼠全身施用TSA-EVs可显著改善骨量。此外，TSA-EVs模拟了运动诱导的EVs的成骨益处，这表明抑制HDAC可以复制运动诱导的对骨骼健康的益处。这些结果表明，TSA诱导的肌肉来源的EVs作为一种治疗策略，在增强骨形成和预防骨质疏松方面具有潜力，特别是对于无法进行运动的人。鉴于各种HDAC抑制剂已获得美国食品药品监督管理局（FDA）的批准，这种方法在骨质疏松治疗的快速临床转化方面具有重大前景。 3.【综述】郑州大学杨帅玺、胡军红、谷晓明：转移前生态位的形成、特征和治疗 Wang, Y., et al. (2024). "Pre-metastatic niche: formation, characteristics and therapeutic implication."  Signal Transduct Target Ther 9(1): 236. IF=40.8 该综述重点关注肿瘤衍生分泌因子、细胞外囊泡和循环肿瘤细胞在形成转移生态位中的作用。 4.中国科学院上海药物研究所甘勇研究员、俞淼荣副研究员与浙江大学胡国庆教授团队合作：胆固醇在外泌体递释RNA药物中的关键作用 Zhuo, Y., et al. (2024). "Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes."  Nat Nanotechnol. IF=38.1 在治疗应用中使用短干扰RNA（siRNA）时，高效的胞质递送是一个重大障碍。该研究表明富含胆固醇的外泌体易于通过膜融合进入癌细胞，实现siRNA的直接胞质递送。分子动力学模拟表明，变形以及与靶细胞膜增加接触有助于膜融合。在体外实验中，与天然的和去除胆固醇的牛奶来源外泌体（MEs）以及传统的转染试剂相比，富含胆固醇的MEs实现了siRNA显著更高的基因沉默效果，诱导了更优的癌细胞凋亡。当对患有原位肿瘤或皮下肿瘤的小鼠进行口服或静脉给药时，富含胆固醇的MEs/siRNA表现出优于脂质纳米颗粒的抗肿瘤活性。总的来说，通过调节外泌体膜的胆固醇含量以促进通过膜融合进入细胞，该研究为基于siRNA的基因治疗提供了一种有前景的方法，为有效、安全和简单的基因治疗策略铺平了道路。 5.南京邮电大学有机电子与信息显示国家重点实验室及化学与生命科学学院汪联辉教授、丁显光教授团队与新加坡国立大学David Tai Leong团队合作：纳米封装的肿瘤囊泡用作自体肿瘤疫苗 Ding, X., et al. (2024). "Non-discriminating engineered masking of immuno-evasive ligands on tumour-derived extracellular vesicles enhances tumour vaccination outcomes."  Nat Nanotechnol. IF=38.1 个性化癌症免疫疗法的成功取决于初始肿瘤抗原向树突状细胞和巨噬细胞的呈递。肿瘤来源的细胞外囊泡（TEVs）含有丰富的肿瘤抗原分子。然而，TEVs 表面存在如分化簇 47（CD47）等抗吞噬信号，这会导致相同的树突状细胞和巨噬细胞无法对其进行吞噬。该研究表明氢氧化铁纳米复合材料可以成功地掩盖 TEV 表面并解除吞噬作用的阻滞，而不影响细胞外囊泡所引发的免疫目标。在被内化后，掩盖物在溶酶体中分解，释放出肿瘤抗原物质。这在动物模型中触发了抗原呈递，并促进了树突状细胞的活化和成熟以及巨噬细胞的重编程，导致肿瘤体积和转移显著减少，在人类恶性胸腔积液临床样本中也是如此。这种直接的掩盖策略消除了临床样本中普遍存在的抗吞噬阻滞，可以普遍应用于所有患者特异性的 TEVs，作为肿瘤抗原剂用于增强免疫治疗。 6.江苏大学张徐、南通大学顾建美、江苏大学李翀：N2 TANs外泌体在体外和体内促进胃癌转移 Zhang, J., et al. (2024). "Exosomal miR-4745-5p/3911 from N2-polarized tumor-associated neutrophils promotes gastric cancer metastasis by regulating SLIT2." Mol Cancer 23(1): 198. IF=27.7 肿瘤细胞重塑肿瘤微环境（TME）细胞的表型和功能，以利于肿瘤进展。先前的研究表明，肿瘤微环境中的中性粒细胞在肿瘤衍生因子的作用下极化为N2肿瘤相关中性粒细胞（TANs），从而促进肿瘤生长、转移、血管生成、治疗抵抗和免疫抑制。外泌体在人类健康和包括癌症在内的疾病中充当关键的细胞间信使。到目前为止，来自N2 TANs的外泌体在胃癌中的生物学作用尚未得到充分表征。该研究首次报告了来自N2 TANs的外泌体在体内外均促进胃癌转移。研究发现来自N2 TANs的外泌体将miR-4745-5p/3911转移到胃癌细胞中，下调SLIT2（slit导向配体2）基因表达。腺病毒介导的SLIT2过表达逆转了N2TANs衍生外泌体对胃癌转移的促进作用。进一步揭示了胃癌细胞通过外泌体HMGB1（高迁移率族蛋白B1）/NF-κB通路诱导中性粒细胞的葡萄糖代谢重编程，该通路介导中性粒细胞N2极化和miR-4745-5p/3911上调。进一步采用微滴式数字PCR（ddPCR）检测人血清样本中N2 TANs外泌体中miR-4745-5p/3911的表达，发现与健康对照者和良性胃病患者相比，胃癌患者中其水平升高。总之，结果表明，N2 TANs通过外泌体miR-4745-5p/3911调节胃癌细胞中的SLIT2促进癌症转移，这为肿瘤微环境细胞衍生外泌体在胃癌转移中的作用提供了新的见解，并为胃癌诊断提供了一个潜在的生物标志物。 7.中国医科大学赵立/刘宏旭研究团队：LAMTOR1降低外泌体PD-L1以增强非小细胞肺癌的免疫治疗效果 Wu, B., et al. (2024). "LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer." Mol Cancer 23(1): 184.IF=27.7 在利用免疫检查点阻断（ICB）治疗非小细胞肺癌（NSCLC）方面已经取得了巨大进展。针对在肿瘤细胞上表达的程序性细胞死亡蛋白1（PD-1）及其配体PD-L1的疗法在提高患者生存率方面显示出潜力。一个未解决的问题涉及肿瘤微环境（TME）中由外泌体PD-L1诱导的免疫抑制，特别是对于CD8(+)T细胞。研究揭示了LAMTOR1在抑制非小细胞肺癌中外泌体PD-L1以及促进CD8(+)T细胞浸润方面的关键作用。通过与HRS相互作用，LAMTOR1促进PD-L1的溶酶体降解，从而减少外泌体PD-L1的释放。值得注意的是，LAMTOR1促进PD-L1溶酶体降解的能力依赖于一个特定的泛素化位点和一个HRS结合序列。研究结果表明，利用LAMTOR1构建肽可能是一种有前景的策略，以增强非小细胞肺癌免疫治疗的疗效。对LAMTOR1如何抑制外泌体PD-L1释放的发现和理解为改善免疫治疗的潜在治疗策略提供了见解。有必要进行进一步的研究和临床试验，以调查在非小细胞肺癌治疗中靶向LAMTOR1的可行性和有效性。 8. 【综述】中南大学刘傥、黎志宏：癌症相关成纤维细胞衍生的细胞外囊泡介导的癌症治疗抵抗——从生物学机制到临床意义及影响 Lin, Z., et al. (2024). "Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications."  Mol Cancer 23(1): 191.IF=27.7 癌症相关成纤维细胞（CAFs）是肿瘤微环境中的一种多样化的基质细胞群体，在癌症进展和患者预后中发挥着基础作用。多项证据表明，CAFs在塑造肿瘤微环境的结构和功能方面起着关键作用，在调节肿瘤行为如转移、侵袭和上皮间质转化（EMT）等方面具有众多功能。CAFs可以通过产生细胞外囊泡（EVs）、多种分泌因子和代谢物与癌细胞广泛相互作用。值得注意的是，CAF衍生的EVs已被确定为癌症治疗抵抗的关键介质，并构成了癌症管理中的新型治疗靶点和生物标志物。本综述旨在总结CAF衍生的EVs在介导癌症对化疗、靶向治疗药物、放疗和免疫治疗的抵抗中的生物学作用和详细分子机制。我们还讨论了CAF衍生的EVs作为癌症临床管理中的新型靶点和临床生物标志物的治疗潜力，从而为提高癌症治疗效果和改善患者预后提供一种新的治疗策略。 9.浙江大学Chen Ting、周建维：揭示细胞外囊泡网络——洞察卵巢癌转移和化疗耐药性 Dai, W., et al. (2024). "Unraveling the extracellular vesicle network: insights into ovarian cancer metastasis and chemoresistance."  Mol Cancer 23(1): 201. IF=27.7 卵巢癌（OC）是最常见且致命的妇科恶性肿瘤之一，其高死亡率主要源于其侵袭性、频繁转移以及对标准疗法的抵抗。最近的研究强调了细胞外囊泡（EVs）在这些过程中的关键作用。EVs由生物体分泌，携带多样且具有生物活性的物质，在细胞间通讯中起着至关重要的作用。在功能上，物质的转移协调了多个过程，不仅积极影响原发性肿瘤，还影响局部和远处的转移前微环境。此外，它们独特的生物学特性使EVs成为新型治疗靶点和有前景的药物递送系统，对癌症患者具有潜在的深远影响。本综述总结了EV生物学的最新进展，深入探讨了EVs促成卵巢癌转移和耐药的复杂机制。它还探索了EVs在卵巢癌临床背景下的最新进展和治疗潜力。尽管已经取得了进展，但卵巢癌中的EV研究仍处于起步阶段。因此，本综述提出了现有研究的局限性，并为未来的研究提供了途径。总之，该综述旨在阐明EVs在卵巢癌中的关键作用，并突出它们在该领域的有前景的潜力。 10. 河北大学李振华团队：通过生物正交代谢工程驱动的细胞外囊泡重定向逆转免疫检查点抑制剂相关的心脏毒性 Fan, M., et al. (2024). "Reversing Immune Checkpoint Inhibitor-Associated Cardiotoxicity via Bioorthogonal Metabolic Engineering-Driven Extracellular Vesicle Redirecting."  Adv Mater: e2412340. IF=27.4 免疫检查点抑制剂（ICIs）引起的心脏毒性与高死亡率相关。T细胞在ICI诱导的心脏损伤中起重要作用。抑制局部T细胞活性被认为是减轻ICI相关心脏毒性的有效策略。肿瘤来源的细胞外囊泡（EVs）通过PD-L1过表达促进免疫抑制。在这项研究中，开发了一种生物正交代谢工程驱动的细胞外囊泡重定向（Biomeder）策略，用于原位工程化具有心肌靶向肽的细胞外囊泡。积累的肿瘤来源的细胞外囊泡（TuEVs）通过增加心肌细胞中的PD-L1水平和/或直接抑制T细胞活性来逆转心脏中的免疫环境。更重要的是，发现TuEVs的重定向进一步破坏了肿瘤中的免疫抑制，这有助于抗肿瘤活性。因此，将TuEVs重定向到心脏同时增强了基于ICI的治疗的抗肿瘤疗效和安全性。此外，Biomeder策略成功扩展到预防ICI诱导的1型糖尿病。这种Biomeder技术是一种用于治疗各种ICI相关不良事件的通用方法。 11. 海军军医大学东方肝胆医院付静：质膜蛋白ADCY7的核易位增强了肝细胞癌中T细胞介导的抗肿瘤免疫 Chen, J., et al. (2024). "Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC."  Gut.IF=23 T细胞介导的反应效力是免疫疗法治疗恶性肿瘤有效性的决定因素；然而，由于广泛的免疫抑制微环境，T细胞疗法在肝细胞癌（HCC）中的临床疗效有限。该研究旨在研究导致肝细胞癌免疫逃逸的关键基因，并提出重塑肝细胞癌微环境的新治疗策略。设计：进行全基因组体内规律间隔成簇短回文重复序列（CRISPR）筛选文库，以确定与免疫耐受相关的关键基因。使用单细胞RNA测序（scRNA-seq）、流式细胞术、肝细胞癌小鼠模型、染色质免疫沉淀和免疫共沉淀来探索腺苷酸环化酶7（ADCY7）在肝细胞癌免疫监测中的功能和机制。结果：全基因组体内CRISPR筛选确定了一种新的免疫调节剂-ADCY7。跨膜蛋白ADCY7通过小窝介导的内吞作用进行亚细胞易位，然后在富含亮氨酸重复序列的蛋白59（LRRC59）和输入蛋白β1（KPNB1）的帮助下易位到细胞核。在细胞核中，它作为CCAAT/增强子结合蛋白α（CEBPA）的转录辅因子，诱导CCL5转录，从而增加CD8(+)T细胞浸润以抑制肝细胞癌进展。此外，ADCY7可以作为外泌体分泌并进入邻近的肿瘤细胞以促进CCL5诱导。具有高ADCY7水平的外泌体促进CD8(+)T细胞在肿瘤内的浸润并抑制肝细胞癌肿瘤生长。结论：该研究描述了ADCY7的非常规功能和亚细胞定位，强调了其在肝细胞癌中T细胞介导的免疫中的关键作用以及作为有前景的治疗靶点的潜力。 12. 南方医科大学基础医学院病理学系梁莉教授团队：TSH/TSHR信号通路促进CD8+ T细胞耗竭和结直肠癌免疫逃逸的分子机制 Zeng, S., et al. (2024). "Local TSH/TSHR signaling promotes CD8(+) T cell exhaustion and immune evasion in colorectal carcinoma."  Cancer Commun (Lond). IF=20.1 背景：肿瘤微环境（TME）中CD8(+)T细胞功能障碍导致肿瘤免疫逃逸和免疫治疗耐受。先前已有报道瘦素、类固醇激素和糖皮质激素等激素对T细胞功能的影响。然而，甲状腺刺激激素（TSH）/甲状腺刺激激素受体（TSHR）信号在CD8(+)T细胞耗竭和肿瘤免疫逃逸中的潜在机制仍知之甚少。本研究旨在探讨TSH/TSHR信号对结直肠癌（CRC）中CD8(+)T细胞功能和免疫逃逸的影响。方法：通过免疫荧光和流式细胞术评估CD8(+)T细胞中TSHR的表达水平。功能研究包括在细胞和小鼠模型中调控TSHR表达以研究其在CD8(+)T细胞中的作用。主要通过RNA测序、蛋白质印迹、染色质免疫沉淀和荧光素酶活性测定获得机制方面的见解。使用免疫荧光、流式细胞术和蛋白质印迹研究结直肠癌组织中TSH和TSHR的来源。结果：TSHR在结直肠癌组织中的癌细胞和CD8(+)T细胞中高表达。TSH/TSHR信号被确定为促进CD8(+)T细胞耗竭的内在途径。在CD8(+)肿瘤浸润淋巴细胞（TILs）中条件性删除TSHR通过蛋白激酶A（PKA）/cAMP反应元件结合蛋白（CREB）信号通路改善效应细胞分化并抑制程序性细胞死亡蛋白1（PD-1）和甲型肝炎病毒细胞受体2（HAVCR2或TIM3）等免疫检查点受体的表达。结直肠癌细胞通过外泌体分泌TSHR以增加CD8(+)T细胞中的TSHR水平，从而导致肿瘤微环境中的免疫抑制。髓源性抑制细胞（MDSCs）是肿瘤微环境中TSH的主要来源。结直肠癌中TSHR的低表达是免疫治疗反应的预测因子。结论：本研究结果强调了内源性TSH/TSHR信号在结直肠癌中CD8(+)T细胞耗竭和免疫逃逸中的作用。TSHR可能适合作为结直肠癌免疫治疗中的预测性和治疗性生物标志物。 13. 南方医科大学陈滨等：载外泌体的新型可注射黏附水凝胶用于血友病关节软骨缺损的整体修复 Yang, Q., et al. (2024). "Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect." Bioact Mater 42: 85-111. IF=18 14. 中南大学湘雅二医院代谢内分泌科袁凌青教授团队：血管壁微环境——内皮细胞源性外泌体通过m6A依赖方式介导褪黑素抑制血管钙化和衰老 Shan, S. K., et al. (2024). "Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner." Bioact Mater 42: 52-67. IF=18 15. 徐州医科大学药学院郑爱萍：Fc增强的外泌体具有更好的上皮层传递和肺分布能力，用于肺部疫苗接种 Meng, F., et al. (2024). "Fc-empowered exosomes with superior epithelial layer transmission and lung distribution ability for pulmonary vaccination."  Bioact Mater 42: 573-586. IF=18 16. 中山大学附属第六医院邱剑光主任、王德娟主任团队联合清华大学深圳国际研究生院徐弢教授团队：生物打印间充质干细胞微纤维来源的细胞外囊泡减轻单侧肾缺血再灌注损伤和纤维化 Guo, Q., et al. (2024). "Bioprinted mesenchymal stem cell microfiber-derived extracellular vesicles alleviate unilateral renal ischemia-reperfusion injury and fibrosis by inhibiting tubular epithelial cells ferroptosis." Bioact Mater 40: 649-664. IF=18 17. 中南大学湘雅医院陈灿：可溶解的微针伤口敷料经皮并持续提供抗炎和促血管生成外泌体用于糖尿病伤口治疗 Cao, Y., et al. (2024). "Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment."  Bioact Mater 42: 32-51. IF=18 18. 中南大学湘雅医院李长俊：衰老的骨髓巨噬细胞通过细胞外囊泡介导的旁分泌衰老来驱动全身衰老和年龄相关功能障碍 Hou, J., et al. (2024). "Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence."  Nat Aging. IF=17 19. 厦门大学颜晓梅：红细胞来源的细胞外小泡通过表面展示唾液酸抑制流感病毒 Cai, N., et al. (2024). "Red Blood Cell-Derived Small Extracellular Vesicles Inhibit Influenza Virus through Surface-Displayed Sialic Acids."  Angew Chem Int Ed Engl: e202413946. IF=16.1 20. 军事科学院军事医学研究院辐射医学研究所岳文：装载干细胞线粒体微泡的水凝胶微针贴片促进慢性伤口愈合 Yao, W. D., et al. (2024). "Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing."  ACS Nano 18(39): 26733-26750. IF=15.8 21. 南京大学宋玉君：工程益生菌时空递送双纳米抗体通过靶向肿瘤源外泌体逆转肿瘤免疫抑制 Qin, S., et al. (2024). "Spatiotemporal Delivery of Dual Nanobodies by Engineered Probiotics to Reverse Tumor Immunosuppression via Targeting Tumor-Derived Exosomes."  ACS Nano 18(39): 26858-26871. IF=15.8 22. 【综述】南方医科大学崔力：肿瘤微环境来源的外泌体——T细胞免疫治疗的双刃剑 Lu, Y., et al. (2024). "Tumor Microenvironment-Derived Exosomes: A Double-Edged Sword for Advanced T Cell-Based Immunotherapy." ACS Nano.IF=15.8 23. 【综述】重庆医科大学刘博：线粒体细胞外囊泡——诊断和治疗肺部疾病的一个有前途的途径 Ding, F., et al. (2024). "Mitochondrial Extracellular Vesicles: A Promising Avenue for Diagnosing and Treating Lung Diseases." ACS Nano 18(37): 25372-25404. IF=15.8 24. 北京上海交通大学医学院附属仁济医院/上海市肿瘤研究所向冬喜：细胞外囊泡液体活检用适配体引导的荧光极化平台 Pham, C. V., et al. (2024). "An aptamer-guided fluorescence polarisation platform for extracellular vesicle liquid biopsy." J Extracell Vesicles 13(9): e12502. IF=15.5 25. 南京师范大学郭志刚团队：氧化应激过程中8-氧鸟嘌呤DNA糖基酶-synaptotagmin 7通路增加细胞外囊泡释放并促进肿瘤转移 Ma, Y., et al. (2024). "The 8-oxoguanine DNA glycosylase-synaptotagmin 7 pathway increases extracellular vesicle release and promotes tumour metastasis during oxidative stress."  J Extracell Vesicles 13(9): e12505.IF=15.5 26. 中山大学孙逸仙纪念医院林天歆、陈长昊：含有整合素α6的细胞外囊泡通过与CD151的相互作用促进淋巴结转移前生态位形成的淋巴重塑 Lin, Y., et al. (2024). "Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151."  J Extracell Vesicles 13(10): e12518.IF=15.5 27. 浙江农业科学院刘燕、鲍国连：外膜囊泡包覆纳米地黄多糖增强对细菌感染的保护性免疫 Huang, Y., et al. (2024). "Enhancing protective immunity against bacterial infection via coating nano-Rehmannia glutinosa polysaccharide with outer membrane vesicles."  J Extracell Vesicles 13(9): e12514.IF=15.5 28. 山东大学刘永军、张娜：靶向glypican-3的巨噬细胞递送载药外泌体在小鼠实体瘤模型中提供了有效的细胞治疗 Liu, J., et al. (2024). "Glypican-3-targeted macrophages delivering drug-loaded exosomes offer efficient cytotherapy in mouse models of solid tumours."  Nat Commun 15(1): 8203. IF=14.7 29. 中国科学院上海药物研究所俞淼荣：内质网靶向递送雷公藤红素和PD-L1 siRNA增强免疫原性细胞死亡和增强癌症免疫治疗 Wang, J., et al. (2024). "Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy." Acta Pharm Sin B 14(8): 3643-3660. IF=14.7 30. 中国医学科学院药物研究所吴练秋：半合成硫酸软骨素CS-semi5上调miR-122-5p，通过p38/MMP13途径对骨关节炎产生治疗作用 Li, X., et al. (2024). "Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p, conferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway."  Acta Pharm Sin B 14(8): 3528-3542. IF=14.7 31. 【综述】四川大学与杜兰大学医学院合作：细胞外囊泡在肺癌治疗中的应用进展 Huang, G., et al. (2024). "Recent advances to address challenges in extracellular vesicle-based applications for lung cancer."  Acta Pharm Sin B 14(9): 3855-3875. IF=14.7 32. 台湾大学&长庚大学：Mir221-和mir222富集的adsc-外泌体通过调节BNIP3-MAP1LC3B-BBC3/PUMA通路减轻PM暴露加重的心脏缺血-再灌注损伤 Lee, T. L., et al. (2024). "Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway."  Autophagy: 1-20. IF=14.6 33. 厦门大学朱志教授课题组：细胞外囊泡的聚糖指纹图谱助力癌症液体活检 Zhang, G., et al. (2024). "Fingerprint Profiling of Glycans on Extracellular Vesicles via Lectin-Induced Aggregation Strategy for Precise Cancer Diagnostics." J Am Chem Soc. IF=14.4 前期报道：JACS｜厦门大学朱志教授团队：细胞外囊泡的聚糖指纹图谱助力癌症液体活检 34. 南京鼓楼医院骨科钱邦平/邱勇教授课题组：强直性脊柱炎中韧带组织转运白介素- 17a的细胞外小泡介导韧带-骨串扰 Wang, K., et al. (2024). "Extracellular Vesicles Derived from Ligament Tissue Transport Interleukin-17A to Mediate Ligament-To-Bone Crosstalk in Ankylosing Spondylitis."  Adv Sci (Weinh): e2406876.IF=14.3 35. 上海交通大学医学院附属第六人民医院急诊医学科傅一牧团队：基因工程化铈外泌体通过重塑免疫微环境和修复 DNA 损伤治疗动脉粥样硬化 Wei, P., et al. (2024). "Gene-Engineered Cerium-Exosomes Mediate Atherosclerosis Therapy Through Remodeling of the Inflammatory Microenvironment and DNA Damage Repair." Small: e2404463. IF=13 前期报道：Small｜上海交通大学傅一牧团队：基因工程化铈外泌体通过重塑免疫微环境和修复 DNA 损伤治疗动脉粥样硬化 36. 宁波市中医院陈宁刚/浙江大学高建青：来自水果、蔬菜和中药的PELNs在生物治疗和药物递送中的研究进展 Zhao, B., et al. (2024). "Exosome-like nanoparticles derived from fruits, vegetables, and herbs: innovative strategies of therapeutic and drug delivery."  Theranostics 14(12): 4598-4621. IF=12.4 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769