Lung tumors

肺肿瘤
  • 文章类型: Journal Article
    目的:研究先天性肺畸形(CLMs)与恶性肿瘤的生物学关系。
    方法:12个CPAM的活检,通过全基因组测序分析了6个叶内测序和2个叶外测序。来自10名患者的血液样本用于确认或排除躯体镶嵌。对于每个畸形样品调用推定的体细胞单核苷酸变体(SNV),并使用从血液中提取的对照DNA样品构建了一个常规小组。随后通过Sanger测序确认了这些变异,并进行了搜索,只要有可能,在病人的血液样本中.
    结果:所有CLM,除了一个CLM,都通过具有基因突变的多个细胞簇表现出基因组不稳定性的特征。在6/20先天性肺畸形中检测到7种肿瘤转化相关SNV。在先前与TERT癌基因上游的5p15.33肺癌相关的区域中,发现了四种在普通人群中非常罕见的SNV。此外,我们发现了错义遗传变异,其致瘤作用是众所周知的,在RET中,FANCA和MET基因。
    结论:95%的CLM基因组不稳定,其中30%与肿瘤发展有关的遗传变异,不管组织病理学如何,是恶性肿瘤的诱发因素,再加上接触致癌物,可能引发恶性肿瘤的发展,并解释CLM和肺癌之间的关联。
    OBJECTIVE: To study the biological relationship between congenital lung malformations (CLMs) and malignancy.
    METHODS: Biopsies of 12 CPAMs, 6 intralobar sequestrations and 2 extralobar sequestrations were analyzed through whole-genome sequencing. Blood samples from 10 patients were used to confirm or exclude somatic mosaicism. Putative somatic Single Nucleotide Variants (SNVs) were called for each malformed sample with a Panel of Normals built with control DNA samples extracted from blood. The variants were subsequently confirmed by Sanger sequencing and searched, whenever possible, in the blood samples of patients.
    RESULTS: All CLMs but one presented a signature of genomic instability by means of multiple clusters of cells with gene mutations. Seven tumor transformation-related SNVs were detected in 6/20 congenital lung malformations. Four very rare in the general population SNVs were found in a region previously linked to lung cancer in 5p15.33, upstream of TERT oncogene. Furthermore, we identified missense genetic variants, whose tumorigenic role is well known, in the RET, FANCA and MET genes.
    CONCLUSIONS: Genomic instability in 95% of CLMs and genetic variants linked to tumor development in 30% of them, regardless of histopathology, are predisposing factors to malignancy, that combined with exposure to carcinogens, might trigger the development of malignancy and explain the association between CLMs and lung cancer.
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  • 文章类型: Journal Article
    肿瘤的位置和类型影响肺癌的预后。原发性中央型肺肿瘤(PCLTs)与不良预后和某些组织学类型相关。本研究旨在全面探索临床和支气管镜评估以诊断PCLT的组织病理学类型,并确定与某些组织学类型相关的因素。
    这是一项观察性横断面研究,定义为与肺门结构直接接触或位于半胸部内部三分之二内的肿瘤。我们收集了人口统计学和临床数据,以及支气管镜检查评估和组织病理学类型的数据。肿瘤分期,上腔静脉综合征的症状,并且还记录了气管旁和隆突下区域的淋巴结肿大。
    在895名患者中,37.87%有原发性肺肿瘤,17.76%被归类为PCLT。值得注意的是,PCLT病例表现出更高的III期比例(28.9%vs.18.3%;p=0.03)和鳞状细胞癌(SCC)组织病理学(37.1%vs.17.2%;p=0.00)与非PCLT病例相比。PCLTs的支气管镜检查结果显示中央气道肿块(25.2%)和远端气道压缩性狭窄(25.2%)。159例PCLT病例的亚组分析确定37.10%为SCC。多变量分析强调管腔内肿块可预测中央SCC(比值比2.075,95%置信区间1.07-3.99;p=0.028)。
    第三阶段的比例,SCC组织病理学类型,PCLT患者的管腔内病变高于非PCLT患者。腔内病变的存在可以预测PCLT患者SCC的组织病理学类型。
    UNASSIGNED: The location and type of a tumor influence the prognosis of lung cancer. Primary Central Lung Tumors (PCLTs) are correlated with poor prognoses and certain histologic types. This study aimed to present a comprehensive exploration of clinical and bronchoscopic assessments for diagnosing the histopathology types of PCLTs and identified the factors associated with certain histologic types.
    UNASSIGNED: This was an observational cross-sectional study of PCLTs, defined as tumors in direct contact with hilar structures or located within the inner two-thirds of the hemithorax. We gathered demographic and clinical data, as well as data on bronchoscopy assessment and histopathology type. Tumor stage, symptoms of superior vena cava syndrome, and enlargement of lymph nodes in the paratracheal and subcarinal regions were also documented.
    UNASSIGNED: Of the 895 patients, 37.87% had primary lung tumors, with 17.76% classified as PCLTs. Notably, PCLT cases exhibited a higher proportion of stage III (28.9% vs. 18.3%; p = 0.03) and Squamous Cell Carcinoma (SCC) histopathology (37.1% vs. 17.2%; p = 0.00) compared with non-PCLT cases. Bronchoscopic findings in PCLTs revealed a predilection for central airway masses (25.2%) and compressive distal airway stenosis (25.2%). Subgroup analysis of 159 PCLT cases identified 37.10% as SCC. Multivariate analysis underscored that intraluminal masses predict central SCC (odds ratio 2.075, 95% confidence interval 1.07-3.99; p = 0.028).
    UNASSIGNED: The proportion of stage III, SCC histopathological type, and intraluminal lesions was higher in patients with PCLT than in non-PCLT cases. The presence of intraluminal lesions can predict the histopathological type of SCC in patients with PCLTs.
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  • 文章类型: Case Reports
    肺部的炎性肌纤维母细胞瘤(IMT)是一种罕见的间充质肿瘤,倾向于在儿童肺部发生更多。在成年人中极为罕见。IMT需要广泛的肺切除术,因为它们通常是局部侵入性的。防止复发的关键是完全切除,手术后预后良好。我们报告了一例肺部炎性假瘤患者。患者是一名27岁的女性,出现干咳。胸部X光片和计算机断层扫描显示左主支气管有病变,左肺几乎完全塌陷。因为手术是必要的,以确定诊断,进行左肺切除术,然后对手术标本进行组织学检查,证实是炎性假瘤.
    Inflammatory myofibroblastic tumors (IMTs) of the lung are a rare type of mesenchymal tumors that tend to occur more in the lungs of children. They are extremely rare in adults. IMTs require extensive pulmonary resection because they are commonly locally invasive. The key to preventing recurrence is complete resection, and the prognosis is excellent after surgery. We report a case of a patient with an inflammatory pseudotumor of the lung. The patient is a 27-year-old female who presented with a dry cough. A chest radiograph and computed tomography showed a lesion in the left main bronchus and near-total left lung collapse. As surgery was necessary to establish the diagnosis, left pneumonectomy was performed followed by a histological examination of the surgical specimen which confirmed inflammatory pseudotumor.
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  • 文章类型: Journal Article
    背景:静脉注射吲哚菁绿(ICG)在肺部肿瘤中积聚,通过荧光光谱测量促进它们的检测。该方法有助于识别肉眼不可见的肿瘤位置。我们的目标是确定在肺切除手术期间准确识别肿瘤的最佳ICG剂量和给药方法,利用新型ICG荧光光谱系统进行精确的肿瘤定位。材料和方法:ICG应溶解在提供的溶液或蒸馏水中,并在手术前约24小时静脉内给药。以0.5mg/kg的初始剂量开始。如果肿瘤检出率不足,剂量可逐渐增加至最大5.0mg/kg,以确定有效肿瘤检测的最佳剂量。手术期间的这种荧光光谱可能会显示在术前评估中未检测到的其他病变。主要终点包括肿瘤定位的正确诊断率。次要终点包括测量肺肿瘤的术中ICG荧光光谱强度,评估腹膜内ICG给药的可操作性和安全性,手术标本中ICG荧光光谱强度的测量,在塌陷和扩张期间肺组织的光谱强度的比较,ICG相机图像与荧光光谱强度之间的相关性,荧光分析结果与组织病理学结果的比较。该试验已在jRCT临床试验注册中心注册,代码为jRCTs011230037。结果与结论:本试验旨在建立一种定位和诊断肺部恶性肿瘤的有效方法。从而潜在地改善手术结果和完善治疗方案。
    Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.
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  • 文章类型: Journal Article
    目的:使用网络分析方法在接受计算机断层扫描(CT)引导微波消融(MWA)的肺部肿瘤患者的症状中探索症状群和相互关系。
    方法:进行了一项纵向研究,并招募了196例接受MWA的肺部肿瘤患者,并在24小时进行了测量,48h,和72小时后MWA。MDAnderson症状量表的中文版和修订的肺癌模块用于评估症状。进行网络分析以探索症状簇和症状之间的相互关系。
    结果:在网络中确定了四个稳定症状社区。危难,减肥,胸闷是中枢症状。危难,体重减轻也是最关键的桥梁症状,其次是咳嗽。三个症状网络在症状中心性方面在时间上是稳定的,全球连通性,和网络结构。
    结论:我们的发现确定了中心症状,桥症状,以及MWA后肺部肿瘤患者症状网络的稳定性。这些网络结果将对未来针对性症状管理干预的发展具有重要意义。未来的研究应集中于开发针对中枢症状和桥梁症状的精确干预措施,以促进患者的健康。
    OBJECTIVE: To explore symptom clusters and interrelationships using a network analysis approach among symptoms in patients with lung tumors who underwent computed tomography (CT)-guided microwave ablation (MWA).
    METHODS: A longitudinal study was conducted, and 196 lung tumor patients undergoing MWA were recruited and were measured at 24 h, 48 h, and 72 h after MWA. The Chinese version of the MD Anderson Symptom Inventory and the Revised Lung Cancer Module were used to evaluate symptoms. Network analyses were performed to explore the symptom clusters and interrelationships among symptoms.
    RESULTS: Four stable symptom communities were identified within the networks. Distress, weight loss, and chest tightness were the central symptoms. Distress, and weight loss were also the most key bridge symptoms, followed by cough. Three symptom networks were temporally stable in terms of symptom centrality, global connectivity, and network structure.
    CONCLUSIONS: Our findings identified the central symptoms, bridge symptoms, and the stability of symptom networks of patients with lung tumors after MWA. These network results will have important implications for future targeted symptom management intervention development. Future research should focus on developing precise interventions for targeting central symptoms and bridge symptoms to promote patients\' health.
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  • 文章类型: Journal Article
    拉曼光谱是一种光学技术,它利用非弹性光散射来响应振动分子产生组织的化学指纹,细胞,和生物流体。拉曼光谱策略产生高水平的化学特异性,而不需要大量的样品制备,允许使用先进的光学工具,如显微镜,光纤,以及在可见和近红外光谱范围内工作的激光器,使它们越来越适合广泛的医疗诊断应用。金属纳米粒子和非线性光学效应可以改善拉曼信号,和优化的光纤拉曼探针可以使实时,在体内,单点观测。此外,通过拉曼测量和其他技术的多模态集成,可以提高诊断速度和空间精度。最近的研究大大有助于提高诊断速度和准确性,使其适合临床应用。肺癌是一种常见的呼吸道恶性肿瘤。然而,使用计算机断层扫描进行检测和筛查经常会发现许多较小的肺结节,从临床角度来看,这使得诊断过程更具挑战性。虽然检测到的大多数小结节是良性的,目前没有直接的方法来确定哪些结节代表非常早期的肺癌.这些小结节的非手术活检样本的正电子发射断层扫描和其他辅助诊断方法检出率低,这可能会导致大量的费用和患者并发症的可能性。虽然某些亚组的患者可以接受治愈性治疗,其他个体预后较差,需要其他治疗干预措施.随着治疗癌症的新方法的出现,比如免疫疗法,这可能会延长患者的生存期,甚至在某些情况下导致完全治愈,对于评估这些新型化合物的有效性,确定最合适的生物标志物和指标至关重要.这将确保准确测量显著的治疗结果。本文综述了拉曼光谱及其在肺部肿瘤诊断和分析中的应用前景。
    Raman spectroscopy is an optical technique that uses inelastic light scattering in response to vibrating molecules to produce chemical fingerprints of tissues, cells, and biofluids. Raman spectroscopy strategies produce high levels of chemical specificity without requiring extensive sample preparation, allowing for the use of advanced optical tools such as microscopes, fiber optics, and lasers that operate in the visible and near-infrared spectral range, making them increasingly suitable for a wide range of medical diagnostic applications. Metal nanoparticles and nonlinear optical effects can improve Raman signals, and optimized fiber optic Raman probes can make real-time, in vivo, single-point observations. Furthermore, diagnostic speed and spatial accuracy can be improved through the multimodal integration of Raman measurements and other technologies. Recent studies have significantly contributed to the improvement of diagnostic speed and accuracy, making them suitable for clinical application. Lung cancer is a prevalent type of respiratory malignancy. However, the use of computed tomography for detection and screening frequently reveals numerous smaller lung nodules, which makes the diagnostic process more challenging from a clinical perspective. While the majority of small nodules detected are benign, there are currently no direct methods for identifying which nodules represent very early-stage lung cancer. Positron emission tomography and other auxiliary diagnostic methods for non-surgical biopsy samples from these small nodules yield low detection rates, which might result in significant expenses and the possibility of complications for patients. While certain subsets of patients can undergo curative treatment, other individuals have a less favorable prognosis and need alternative therapeutic interventions. With the emergence of new methods for treating cancer, such as immunotherapies, which can potentially extend patient survival and even lead to a complete cure in certain instances, it is crucial to determine the most suitable biomarkers and metrics for assessing the effectiveness of these novel compounds. This will ensure that significant treatment outcomes are accurately measured. This review provides a comprehensive overview of the prospects of Raman spectroscopy and its applications in the diagnosis and analysis of lung tumors.
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  • 文章类型: Case Reports
    原发性肺滑膜肉瘤(PPSS)可以起源于支气管壁的血管,肺间质,和间隙成分,占所有原发性肺部恶性肿瘤的0.1%-0.5%,最常见的症状是胸痛,咳嗽,呼吸困难,还有咯血.
    滑膜肉瘤(SS)是一种罕见的间质来源的恶性肿瘤,约占所有软组织肉瘤的8%-10%。原发性肺滑膜肉瘤(PPSS)可以起源于支气管壁的血管,肺间质,和间隙成分,占所有原发性肺部恶性肿瘤的0.1%-0.5%。患者的担忧:我们报告了第一例57岁的男性,在手术后诊断为右肺中叶的PPSS的最初表现。诊断:胸部计算机断层扫描(CT)显示右肺中叶肿块,手术切除后经病理诊断为单相SS。干预措施:术前胸腔闭式引流10天后,进行了右胸切开术,以切除肺的右中叶。转归:患者恢复顺利,术后无其他治疗出院。术后7个月的胸部CT随访显示肺内复发伴多发转移。教训:肺的单相PPSS可能以血性胸腔积液为首发表现。
    UNASSIGNED: Primary pulmonary synovial sarcoma (PPSS) can originate from blood vessels of the bronchial wall, lung interstitium, and interstitial components, and accounts for 0.1%-0.5% of all primary lung malignancies, the most common symptoms are chest pain, cough, dyspnea, and hemoptysis.
    UNASSIGNED: Synovial sarcoma (SS) is a rare malignant tumor of stromal origin, which accounts for approximately 8%-10% of all soft tissue sarcomas. Primary pulmonary synovial sarcoma (PPSS) can originate from blood vessels of the bronchial wall, lung interstitium, and interstitial components, and accounts for 0.1%-0.5% of all primary lung malignancies. Patient concerns: We report the first case of a 57-year-old man with bloody pleural effusion as an initial manifestation of PPSS in the middle lobe of the right lung diagnosed after surgery. Diagnosis: Chest computed tomography (CT) revealed a mass in the middle lobe of the right lung, which was pathologically diagnosed as a monophasic SS after surgical resection. Interventions: Ten days after preoperative closed chest drainage, a right thoracotomy was performed to remove the right middle lobe of the lung. Outcomes: The patient recovered smoothly and was discharged from the hospital without any other postoperative treatment. A follow-up chest CT scan 7 months postoperatively revealed intrapulmonary recurrence with multiple metastases. Lessons: Monophasic PPSS of the lung may present with bloody pleural effusion as its first manifestation.
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  • 文章类型: Journal Article
    背景:没有关于COVID-19大流行对肺部患者延迟诊断和治疗的实际影响的最新国家数据,头,和巴西的颈部癌症。本研究旨在分析COVID-19大流行对肺癌诊断和临床结局的影响,头部,和颈部癌症患者在巴西东南部的三级癌症中心得到帮助,以及分析这些患者的预处理临床特征。
    方法:回顾性队列研究了2019年1月至2021年12月在巴西东南部三级癌症中心协助治疗的肺癌或头颈部癌患者。评估组间的统计差异[即,2019年队列与(与)2020年和2019年与2021]卡方检验采用5%显著性水平和90%幂计算样本量。通过两个样本的T检验或Fisher或Pearson卡方检验(定量或定性变量)评估基线临床特征和社会人口统计学特征之间的差异。所有使用的测试具有5%的显著性水平。
    结果:纳入了652例患者,332例肺癌和320例头颈部癌;观察到肺癌患者的肿瘤治疗建议显着减少,姑息治疗建议增加。尽管诊断阶段相似。在COVID-19大流行期间,头颈部癌症患者在首次肿瘤学评估时报告了更多的疼痛症状(p<0.05).与2019年相比,2021年诊断的头颈部癌症患者的初始表现较差(p=0.008)。与2019年相比,2021年被诊断为头颈癌的患者的生存率有统计学上的显着提高(p=0.003)。
    结论:这项研究强调了巴西肺癌和头颈癌患者的低生存率,甚至在大流行开始之前,由于公共卫生系统诊断时的晚期疾病和临床退化特征。此外,尽管临床分期无差异,但肺癌和头颈癌的发病率均有增加.这反映出,在面临COVID-19大流行等急性公共卫生危机之前,公共医疗系统是多么脆弱。然而,对公共卫生的总体影响可能会持续多年。
    BACKGROUND: There is no updated national data regarding the real impact of the COVID-19 pandemic on delaying diagnosis and treatment among patients with lung, and head, and neck cancers in Brazil. This study aimed to analyze the COVID-19 pandemic impact on cancer diagnosis and clinical outcomes among lung, head, and neck cancer patients assisted in a tertiary cancer center in Southeastern Brazil, as well as to analyze these patients\' pretreatment clinical features.
    METHODS: Retrospective cohort of patients with lung or head and neck cancer assisted in a tertiary cancer center in southeastern Brazil between January/2019 and December/2021. To assess statistical differences among groups [i.e., cohort 2019 versus (vs.) 2020 and 2019 vs. 2021] chi-square test was used with a 5% significance level and 90% power for sample size calculation. Differences among baseline clinical features and sociodemographic characteristics were evaluated either by T-test for two samples or Fisher\'s or Pearson\'s chi-square test (for quantitative or qualitative variables). All utilized tests had a 5% significance level.
    RESULTS: Six hundred fifty-two patients were included, 332 with lung and 320 with head and neck cancer; it was observed a significant decrease in oncologic treatment recommendations and increase in palliative care recommendation for patients with lung cancer, despite similar stages at diagnosis. During the COVID-19 pandemic, more pain symptoms were reported at the first Oncology assessment for patients with head and neck cancer (p < 0.05). Compared to 2019, head and neck cancer patients diagnosed in 2021 presented a worse initial performance status (p = 0.008). There was a statistically significant increase in survival for patients diagnosed with head and neck cancer in 2021 when compared to 2019 (p = 0.003).
    CONCLUSIONS: This research highlights low survival rates for patients with lung and head and neck cancer in Brazil, even before the pandemic started, as consequence of advanced diseases at diagnosis at the public health system and clinical degrading features. Additionally, there was an increase incidence in both lung cancer and head and neck cancer despite no differences in clinical stage. This reflects how fragile is the public healthcare system even before facing an acute public health crisis such as the COVID-19 pandemic. Yet, the total impact on public health may follow for many years.
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  • 文章类型: Journal Article
    背景:肺肿瘤是与高死亡率相关的常见恶性肿瘤,造成重大的医疗和社会负担。尽管免疫疗法显示出改善生存率的希望,反应率相对适中。热消融不仅可以直接消除肿瘤细胞,还可以增强抗肿瘤免疫反应,因此表现出与免疫治疗协同作用的显著倾向。
    结论:在这篇综述中,我们简要概述了热消融在周围型肺肿瘤中的应用.我们总结了热消融的患者选择。我们强调了热消融增强抗肿瘤免疫反应的潜力,为联合疗法提供了一个有希望的途径。我们总结了评估热消融和免疫治疗在临床前和临床环境中的协同作用的研究。最后,我们强调了在将热消融和免疫疗法应用于肺部肿瘤患者时需要深入探索的紧迫问题.
    结论:这篇综述强调了在周围型肺肿瘤患者中使用热消融联合免疫治疗的前景。然而,需要进一步的研究来加强和优化这种治疗策略.
    BACKGROUND: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy.
    CONCLUSIONS: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients.
    CONCLUSIONS: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.
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  • 文章类型: Journal Article
    背景:据报道CD93促进肿瘤血管生成。然而,CD93是否调节抗肿瘤免疫仍不清楚。方法:肺肿瘤组织,恶性胸腔积液(MPEs)来自肺癌患者.从健康志愿者和接受抗PD-1治疗的肺癌患者获得血液。此外,p53fl/flLSL-KrasG12D,Ccr7-/-,产生Cd93-/-小鼠和CD11c-DTR小鼠。具体来说,EM,利用NTA和蛋白质印迹来鉴定肿瘤细胞外囊泡(TEV)。EV标签,体外和体内EV摄取的检测,进行EV蛋白和RNA的降解以检测TEV在肿瘤进展中的作用。分离胸膜间皮细胞(pMCs)以研究相关的信号通路。产生重组蛋白和抗体以测试哪种抗体是最有效的抗体以增加p-pMC中的CCL21a。RNA-Seq,miRNA阵列,荧光素酶报告分析,内皮管形成试验,蛋白质标记和检测,siRNA和miRNA模拟物和抑制剂的转染,趋化性测定,免疫组织化学染色,流式细胞术,实时PCR,进行ELISA实验。结果:我们显示pMC的CD93通过阻止pMC分泌CCL21来减少树突状细胞的肺肿瘤迁移,从而抑制系统性抗肺肿瘤T细胞反应。TEV衍生的miR-5110通过下调pMCCD93促进CCL21分泌,而C1q,在肿瘤个体中增加,抑制CD93介导的CCL21分泌。CD93阻断抗体(抗CD93)比VEGF受体阻断抗体更好地抑制肺肿瘤生长,因为抗CD93抑制肿瘤血管生成并促进CCL21从pMC分泌。抗CD93还克服了肺肿瘤对抗PD-1疗法的抗性。此外,血清EV来源的miR-5193(人miR-5110同源物)较高的肺癌患者对抗PD-1治疗更敏感,而血清C1q较高的患者不太敏感,与它们对CD93的调节功能一致。结论:我们的研究确定了CD93在控制抗肺肿瘤免疫中的关键作用,并为肺肿瘤治疗提供了有希望的方法。
    Background: CD93 reportedly facilitates tumor angiogenesis. However, whether CD93 regulates antitumor immunity remains undeciphered. Methods: Lung tumor tissues, malignant pleural effusions (MPEs) were obtained from lung cancer patients. Blood was obtained from healthy volunteers and lung cancer patients with anti-PD-1 therapy. Furthermore, p53fl/flLSL-KrasG12D, Ccr7-/-, Cd93-/- mice and CD11c-DTR mice were generated. Specifically, EM, NTA and western blotting were utilized to identify Tumor extracellular vesicles (TEVs). EV labeling, detection of EV uptake in vitro and in vivo, degradation of EV proteins and RNAs were performed to detect the role of TEVs in tumor progression. Pleural mesothelial cells (pMCs) were isolated to investigate related signaling pathways. Recombinant proteins and antibodies were generated to test which antibody was the most effective one to increase CCL21a in p-pMCs. RNA-Seq, MiRNA array, luciferase reporter assay, endothelial tube formation assay, protein labeling and detection, transfection of siRNAs and the miRNA mimic and inhibitor, chemotaxis assay, immunohistochemical staining, flow cytometry, Real-time PCR, and ELISA experiments were performed. Results: We show that CD93 of pMCs reduced lung tumor migration of dendritic cells by preventing pMCs from secreting CCL21, thereby suppressing systemic anti-lung tumor T-cell responses. TEV-derived miR-5110 promotes CCL21 secretion by downregulating pMC CD93, whereas C1q, increasing in tumor individuals, suppresses CD93-mediated CCL21 secretion. CD93-blocking antibodies (anti-CD93) inhibit lung tumor growth better than VEGF receptor-blocking antibodies because anti-CD93 inhibit tumor angiogenesis and promote CCL21 secretion from pMCs. Anti-CD93 also overcome lung tumor resistance to anti-PD-1 therapy. Furthermore, lung cancer patients with higher serum EV-derived miR-5193 (human miR-5110 homolog) are more sensitive to anti-PD-1 therapy, while patients with higher serum C1q are less sensitive, consistent with their regulatory functions on CD93. Conclusions: Our study identifies a crucial role of CD93 in controlling anti-lung tumor immunity and suggests a promising approach for lung tumor therapy.
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