Adenocarcinoma

腺癌
  • 文章类型: Case Reports
    小肠腺癌(SBA)很少见,消化系统隐匿性和危及生命的恶性肿瘤。鉴于低发病率和非特异性症状,SBA经常在后期阶段被检测到。双对比增强超声(DCEUS)是一种应用于胃肠道可视化的创新成像技术,合并静脉超声造影和口腔超声造影。在这种情况下,利用DCEUS并成功检测到空肠的SBA。
    一个中国女人,64岁,在我们医院的消化内科寻求咨询,报告腹痛症状。进医院前三个月,她接受了胃镜和结肠镜检查,提示慢性胃炎,她接受了口服药物治疗.然而,她的症状没有缓解,甚至恶化。为了进一步调查,进行了DCEUS。口服造影剂扩张了上消化道的管腔,解决由胃肠道中的气体引起的障碍,并创建用于扫描的声学窗口。通过这个声音窗口,口服造影剂超声造影(OA-CEUS)显示空肠肠壁局部增厚,尺寸为4x3cm。静脉注射超声造影剂后,空肠病变表现出更快的增强和异质的过度增强。最后,患者接受了空肠肿瘤切除术。病理检查发现空肠腺癌。
    SBA的及时诊断可能具有挑战性。DCEUS可能有助于SBA的诊断和详细评估,特别是在涉及空肠的情况下。需要进一步的研究来充分探索DCEUS在小肠疾病的标准诊断方法中的益处。
    UNASSIGNED: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum.
    UNASSIGNED: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma.
    UNASSIGNED: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    二硫化物下垂,一种受调节的细胞死亡形式,最近报道了以SLC7A11高表达为特征的癌症,包括浸润性乳腺癌,肺腺癌,和肝细胞癌。然而,它在结肠腺癌(COAD)中的作用很少被讨论。在这项研究中,我们使用LASSO和Cox回归分析,建立并验证了基于20个二硫键下垂相关基因(DRGs)的预后模型.通过列线图评估了该模型的鲁棒性和实用性。随后的相关性和富集分析揭示了风险评分之间的关系,几个关键的癌症相关的生物过程,免疫细胞浸润,以及癌基因和细胞衰老相关基因的表达。POU4F1,我们模型的重要组成部分,由于其在COAD肿瘤中的上调及其与癌基因表达的正相关,因此可能充当癌基因。体外实验表明,POU4F1敲低可显著降低COAD细胞的细胞增殖和迁移,但增加细胞衰老。我们通过在葡萄糖剥夺的培养基中培养细胞,进一步研究了DRG在二硫键下垂中的调节作用。总之,我们的研究揭示并证实了基于DRG的COAD患者风险预测模型,并验证了POU4F1在促进细胞增殖中的作用,迁移,和二硫化物下垂。
    Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    通过可解释的深度学习在结肠组织中早期发现腺癌,通过对组织学图像进行分类,并在模型预测上提供视觉可解释性。考虑到近年来,深度学习技术已经成为医学图像分析中的强大技术,提供前所未有的准确性和效率,在本文中,我们提出了一种自动检测结肠组织图像中癌细胞存在的方法。考虑了各种深度学习架构,目的是在定量和定性结果方面考虑最佳结果。事实上,我们通过考虑所谓的预测可解释性来考虑定性结果,通过提供一种在组织图像上突出显示从模型角度来看与结肠癌存在相关的区域的方法。实验分析,在10,000个结肠问题图像上执行,通过获得等于0.99的精度,证明了该方法的有效性。实验分析表明,所提出的方法可以成功地用于从组织图像中检测和定位结肠癌。
    Early detection of the adenocarcinoma cancer in colon tissue by means of explainable deep learning, by classifying histological images and providing visual explainability on model prediction. Considering that in recent years, deep learning techniques have emerged as powerful techniques in medical image analysis, offering unprecedented accuracy and efficiency, in this paper we propose a method to automatically detect the presence of cancerous cells in colon tissue images. Various deep learning architectures are considered, with the aim of considering the best one in terms of quantitative and qualitative results. As a matter of fact, we consider qualitative results by taking into account the so-called prediction explainability, by providing a way to highlight on the tissue images the areas that from the model point of view are related to the presence of colon cancer. The experimental analysis, performed on 10,000 colon issue images, showed the effectiveness of the proposed method by obtaining an accuracy equal to 0.99. The experimental analysis shows that the proposed method can be successfully exploited for colon cancer detection and localisation from tissue images.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:这项研究描述了一个大型的,来自单个巴西中心的唾液腺多形性腺癌(PAC)的有据可查的病例系列。
    方法:人口统计数据,临床表现,对26例PAC的组织病理学和免疫组织化学特征进行了详细的分析和讨论。
    结果:大多数患者为女性(n=21),比例为1:4.2(男性:女性),平均年龄为58.8岁(36至84岁)。最常见的临床表现是纤维胶原,结节性病变,平均尺寸为2.46厘米(范围从0.5到3厘米)。大多数病变发生在腭(n=16),其次是颊粘膜(n=3),上唇(n=3),颊前庭(n=2)和牙槽(n=1)。组织学上,观察到各种生长模式,包括管状,固体,cribriform,乳头状,和囊性的。此外,肾小球样裂隙状结构,粘液,并注意到透明细胞。在少数情况下观察到表面乳头状上皮增生。9例表现为黏液样和胶原区,两例显示梭形区域,另一例显示鳞状分化。在两种情况下都注意到透明细胞优势,8例出现神经周和神经内侵袭。免疫组织化学分析显示,在所有情况下,S-100,p63和CK7均为阳性,p40均为阴性。Ki-67增殖指数在大多数情况下明显较低,平均值为2.5%。
    结论:我们提供了广泛的,PAC的临床和微观特征的详细描述,巴西队列。这些发现,在资源有限的地区,可能对建立正确的诊断非常有用。
    OBJECTIVE: This study describes a large, well-documented case series of salivary gland polymorphous adenocarcinomas (PAC) from a single Brazilian center.
    METHODS: Demographic data, clinical presentation, histopathological and immunohistochemical features from 26 cases of PAC were analyzed and discussed in detail.
    RESULTS: Most patients were females (n = 21), with a ratio of 1:4.2 (male: female) with a mean age of 58.8 years (ranging from 36 to 84 years). The most common clinical presentation was a fibrocollagenous, firm nodular lesion, with a mean size of 2.46 cm (ranging from 0.5 to 3 cm). Most lesions occurred on the palate (n = 16), followed by buccal mucosa (n = 3), upper lip (n = 3), buccal vestibule (n = 2) and alveolar ridge (n = 1). Histologically, various growth patterns were observed, including tubular, solid, cribriform, papillary, and cystic. Additionally, glomeruloid slit-like structures, mucous, and clear cells were noted. Surface papillary epithelial hyperplasia was observed in a few cases. Nine cases exhibited myxoid and collagenous areas, while two cases showed fusiform areas and another case demonstrated squamous differentiation. Clear cell predominance was noted in two cases, and peri- and intraneural invasion was seen in eight cases. Immunohistochemical analysis revealed positivity for S-100, p63 and CK7, and negativity for p40 in all cases. The Ki-67 proliferation index was markedly low in most cases, with a mean of 2.5%.
    CONCLUSIONS: We have provided a broad, detailed description of the clinical and microscopic features of PAC in a large, Brazilian cohort. These findings, in a resource-limited area, may be quite useful for establishing a proper diagnosis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Editorial
    分子医学在理解疾病机制和发现目标干预措施方面开辟了新的视野。更广泛的DNA和RNA测序,免疫组织化学分析,蛋白质组学,和其他分子测试改变了医生管理疾病的方式。癌症基因组图谱计划提出的胃癌分子分类将胃腺癌分为四种亚型。然而,批准临床使用的可用靶标和/或免疫疗法似乎与这些分子亚型分离。直到对分子分类提供的大量数据进行更可靠的解释,在分子治疗时代,临床指南将依靠可用的可操作靶点和已批准的治疗方法来指导临床医生进行癌症治疗.
    Molecular medicine opened new horizons in understanding disease mechanisms and discovering target interventions. The wider availability of DNA and RNA sequencing, immunohistochemical analysis, proteomics, and other molecular tests changed how physicians manage diseases. The gastric cancer molecular classification proposed by The Cancer Genome Atlas Program divides gastric adenocarcinomas into four subtypes. However, the available targets and/or immunotherapies approved for clinical use seem to be dissociated from these molecular subtypes. Until a more reliable interpretation of the stupendous amount of data provided by the molecular classifications is presented, the clinical guidelines will rely on available actionable targets and approved therapies to guide clinicians in conducting cancer management in the era of molecular therapies.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:尽管胃癌的多模式治疗具有优势,放弃化疗治疗以及对阻塞患者进行前期手术的需要对治疗产生负面影响。在巴西统一国家卫生系统(SUS)方案中,在专门中心获得治疗的困难是一个加重因素。
    目标:为了确定优势,预后因素,并发症,在SUS环境中胃癌治疗的新辅助和辅助治疗生存率。
    方法:回顾性研究包括81例胃腺癌患者,这些患者根据INT0116试验(辅助放化疗)接受了治疗,经典试验(辅助化疗),FLOT4-AIO试验(围手术期化疗),以及2015年至2020年在单个癌症中心进行的治愈意向手术(R0切除和D2淋巴结清扫术)。具有其他组织学类型的个体,胃残端,食道癌,其他治疗方案,并排除Ia或IV期。
    结果:患者分为FLOT4-AIO(26例),经典(25名患者),INT0116(30名患者)。平均年龄为61岁。60%以上的患者有病理III期。治疗完成率为56%。FLOT4-AIO组病理完全缓解率为7.7%。影响总体生存率和无病生存率的预后因素包括酒精中毒,术后早期并发症,和解剖病理学状态pN2和pN3。3年总生存率为64.9%,CLASSIC亚组生存率最好(79.8%)。
    结论:胃癌的治疗策略因初次手术的需要而异。CLASSIC亚组具有更好的总生存率和无病生存率。INT0116方案还可以预防死亡率,但没有统计学意义。尽管FLOT4-AIO是首选治疗方法,在SUS方案中进行新辅助治疗的困难对结果有负面影响,因为食物摄入的重要性和治疗耐受性较差.
    BACKGROUND: Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor.
    OBJECTIVE: To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting.
    METHODS: The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded.
    RESULTS: Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%).
    CONCLUSIONS: The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    该研究试图确定三级机构中一组肺癌患者的临床特征和组织学亚型。
    回顾性回顾3年期间在呼吸道诊所的组织学确诊肺癌病例的医疗记录。
    呼吸诊所,Korle-Bu教学医院,阿克拉,加纳。
    纳入所有经组织学诊断为肺癌的成年患者。
    肺癌组织学类型。
    肺癌病例比例为12.4%。大多数为女性(57.8%),诊断时的平均年龄为55.8±16.0岁。患者主要是非吸烟者(61%)。常见症状为慢性咳嗽和胸痛。超过三分之二的病例出现在临床III和IV期,主要的组织学亚型是吸烟者和非吸烟者的腺癌。对表皮生长因子受体(EGFR)和间变性淋巴瘤激酶(ALK)突变的基因检测基本上不存在。
    大多数肺癌患者晚期疾病。腺癌是主要的非吸烟人群的主要组织学亚型,在不到60岁的女性中患病率增加。这应该鼓励检测基因突变,以提高患者的生存率。
    没有声明。
    UNASSIGNED: The study sought to determine clinical characteristics and histologic subtypes of a cohort of lung cancer patients in a tertiary facility.
    UNASSIGNED: Retrospective review of the medical records of histology-confirmed lung cancer cases at the respiratory clinic over a 3-year period.
    UNASSIGNED: Respiratory Clinic, Korle-Bu Teaching Hospital, Accra, Ghana.
    UNASSIGNED: All adult patients with histologically diagnosed lung cancer were enrolled.
    UNASSIGNED: Lung cancer histological types.
    UNASSIGNED: The proportion of lung cancer cases was 12.4%. The majority were women (57.8%) and the mean age at diagnosis was 55.8±16.0 years. The patients were predominantly non-smokers (61%). Common symptoms were chronic cough and chest pain. More than two-thirds of the cases presented in clinical stages III and IV with the predominant histological subtype being adenocarcinoma in smokers and non-smokers. Genetic testing for epidermal growth factor receptor (EGFR) and Anaplastic Lymphoma kinase (ALK) mutations were largely absent.
    UNASSIGNED: The majority of lung cancer patients presented late with advanced disease. Adenocarcinoma was the predominant histological subtype in a predominantly non-smoking population, with an increased prevalence among women less than 60 years. This should encourage testing for genetic mutations to improve patient survival.
    UNASSIGNED: None declared.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:食管癌和贲门腺癌在中国南方潮汕地区发病率较高。多灶性食管癌和贲门癌(MECC)在临床实践中通常在该地区观察到。然而,MECC的基因组特征仍不清楚.
    方法:在本研究中,总共分析了2123例EC和GCA的临床样本,以确定多灶性肿瘤的频率,以及它们的发生部位和病理类型。Cox比例风险回归用于建立年龄之间的关系模型,性别,在我们对541例患者队列的分析中,肿瘤状态与生存有关,有可用的随访数据。我们对10例MECC患者的20个肿瘤病灶和10个正常样本进行了全基因组测序,以推断6例MECC患者的克隆结构,以探索基因组特征。
    结果:EC和GCA的MECC率为5.65%(2123中的121)。年龄和性别是可能影响MECC风险的潜在因素(p<0.001)。此外,与单肿瘤患者相比,MECC患者的生存率较差。我们发现6例患者的12个病灶是多中心起源模型(MC),与转移模型相比,其在成对病灶中表现出明显的异质性,并且免疫基因中的种系突变数量增加。在MC案例中,同一患者的不同病变由不同的突变和拷贝数变异(CNV)事件驱动.尽管TP53和其他驱动突变基因在样本中的频率很高,它们的突变位点在配对肿瘤标本中显示出显著的异质性.另一方面,CNV基因在配对样本中表现出更高的一致性,特别是在癌基因的扩增和抑癌基因的缺失方面。
    结论:肿瘤间异质性的程度表明MECC的单克隆和多克隆起源,这可以深入了解MECC的基因组多样性并指导临床实施。
    BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear.
    METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics.
    RESULTS: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes.
    CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    考虑到来自不同社会经济背景的患者可能暴露于不同风险因素的可能性,研究了来自不同社会经济背景的秘鲁胃腺癌患者的基因组特征。我们在秘鲁的两个城市(利马和伊卡)进行了一项前瞻性试点研究。这项研究招募了15名来自低社会经济地位(LSES)的患者和15名来自中/高社会经济地位(MHSES)的患者。胃腺癌样品的基因组分析通过FoundationOneCDx平台进行。我们比较了LSES和MHSES的基因组特征以及对靶向治疗和免疫治疗的需求。改变率较高的基因是TP53(73.3%vs.50.0%,P=0.2635);CDH1(26.7%vs.28.6%,P=1);CDKN2A(20.0%vs.28.6%,P=1);KRAS(33.3%vs.7.1%,P=0.1686);ARID1A(20.0%vs.14.3%,P=1);MLL2(13.3%vs.21.4%,P=1)和SOX9(33.3%与0.0%,P=0.0421)在LSES与HMSES中,分别。肿瘤突变负荷(P=0.377)或微卫星状态(P=1)没有显着差异。根据基因参与和改变,LSES组对靶向治疗或免疫疗法的需求更高。不同社会经济地位的胃腺癌患者之间存在显著的基因组差异,这可能导致对靶向治疗和免疫疗法的不同需求。
    The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:三级淋巴结构(TLSs)被认为可以刺激抗肿瘤免疫,并对预后和对免疫检查点阻断的反应产生积极影响。在胃癌(GC)中,然而,TLS主要在GC中发现,预后差,治疗反应有限。我们,因此,假设TLS的免疫细胞组成和功能取决于肿瘤位置和肿瘤免疫环境。
    方法:使用来自GC原发肿瘤和腹膜转移的档案切除标本,使用空间转录组学和免疫组织化学来表征TLS内外CD45免疫细胞的表型。
    结果:我们确定了GC中TLS的细胞组成和成熟状态的显着患者内部和患者间多样性。肿瘤位置(原发与转移部位)占TLS成熟度的大多数差异,因为腹膜转移瘤中的TLS主要是未成熟的。与具有成熟TLS的肿瘤相比,这与更高水平的肿瘤浸润巨噬细胞和Treg以及更少的浆细胞有关。此外,成熟的TLS的特征是抗肿瘤免疫途径如B细胞相关途径的过度表达,MHCII类抗原呈递,而未成熟的TLS与蛋白途径相关,包括T细胞耗尽和相应癌症中DNA修复途径的增强。
    结论:观察到GC来源的腹膜转移通常含有未成熟的TLS,这些TLS与免疫抑制性调节性肿瘤浸润的白细胞有关,与缺乏对免疫检查点阻断的反应和腹膜转移性GC的不良预后特征保持一致,在优化转移性GC的免疫调节策略时需要考虑这一点。
    BACKGROUND: Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in GC with poor prognosis and limited treatment response. We, therefore, hypothesize that immune cell composition and function of TLS depends on tumor location and the tumor immune environment.
    METHODS: Spatial transcriptomics and immunohistochemistry were used to characterize the phenotype of CD45+ immune cells inside and outside of TLS using archival resection specimens from GC primary tumors and peritoneal metastases.
    RESULTS: We identified significant intrapatient and interpatient diversity of the cellular composition and maturation status of TLS in GC. Tumor location (primary vs metastatic site) accounted for the majority of differences in TLS maturity, as TLS in peritoneal metastases were predominantly immature. This was associated with higher levels of tumor-infiltrating macrophages and Tregs and less plasma cells compared with tumors with mature TLS. Furthermore, mature TLSs were characterized by overexpression of antitumor immune pathways such as B cell-related pathways, MHC class II antigen presentation while immature TLS were associated with protumor pathways, including T cell exhaustion and enhancement of DNA repair pathways in the corresponding cancer.
    CONCLUSIONS: The observation that GC-derived peritoneal metastases often contain immature TLS which are associated with immune suppressive regulatory tumor-infiltrating leucocytes, is in keeping with the lack of response to immune checkpoint blockade and the poor prognostic features of peritoneal metastatic GC, which needs to be taken into account when optimizing immunomodulatory strategies for metastatic GC.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号