cancer vaccines

癌症疫苗
  • 文章类型: Journal Article
    尽管对基于纳米医学的癌症免疫疗法的研究越来越多,该领域的总体研究趋势仍未得到充分表征。本研究旨在通过文献计量分析,评估基于纳米医学的癌症免疫治疗的研究趋势和热点。截至2024年3月31日,相关出版物已从WebofScienceCoreCollection中检索到。分析工具包括VOSviewer,CiteSpace,并采用在线文献计量分析平台。总共分析了5,180种出版物。这项研究揭示了研究产出的地理差异,中国和美国是主要的贡献者。在制度上,中国科学院,中国科学院大学,四川大学是杰出的贡献者。作者分析确定了关键研究人员,刘壮是最多产的作家。“ACSNano”和“控释和生物材料杂志”被确定为该领域的领先期刊。经常出现的关键词包括“癌症免疫疗法”和“药物递送”。“该领域的新兴前沿,如“mRNA疫苗,“”声动力疗法,口腔鳞状细胞癌,\"\"STING途径,“和”cGAS-STING途径,“正在经历快速增长。这项研究旨在为推进基于纳米医学的癌症免疫治疗的科学研究和临床应用提供新的见解。
    Despite the increasing number of studies on nanomedicine-based cancer immunotherapy, the overall research trends in this field remain inadequately characterized. This study aims to evaluate the research trends and hotspots in nanomedicine-based cancer immunotherapy through a bibliometric analysis. As of March 31, 2024, relevant publications were retrieved from the Web of Science Core Collection. Analytical tools including VOSviewer, CiteSpace, and an online bibliometric analysis platform were employed. A total of 5,180 publications were analyzed. The study reveals geographical disparities in research output, with China and the United States being the leading contributors. Institutionally, the Chinese Academy of Sciences, University of Chinese Academy of Sciences, and Sichuan University are prominent contributors. Authorship analysis identifies key researchers, with Liu Zhuang being the most prolific author. \"ACS Nano\" and the \"Journal of Controlled Release and Biomaterials\" are identified as the leading journals in the field. Frequently occurring keywords include \"cancer immunotherapy\" and \"drug delivery.\" Emerging frontiers in the field, such as \"mRNA vaccine,\" \"sonodynamic therapy,\" \"oral squamous cell carcinoma,\" \"STING pathway,\"and \"cGAS-STING pathway,\" are experiencing rapid growth. This study aims to provide new insights to advance scientific research and clinical applications in nanomedicine-based cancer immunotherapy.
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  • 文章类型: Journal Article
    肿瘤疫苗通过引发针对肿瘤的抗原特异性应答而成为癌症治疗的有希望的方法。然而,自噬和免疫抑制肿瘤微环境(TME)减少抗原暴露和免疫原性,这限制了肿瘤疫苗的效果。这里,我们开发了基于岩藻依聚糖(Fuc)的二氢卟啉e6(Ce6)-氯喹(CQ)自组装水凝胶(CCFG)作为原位疫苗。Ce6通过光动力疗法(PDT)诱导的免疫原性细胞死亡(ICD)效应触发原位免疫反应,Fuc的巨噬细胞极化和CQ的自噬抑制进一步增强。体内研究表明,CCFG在激光照射下有效增强抗原呈递,诱导强大的原位疫苗作用,并显着抑制肿瘤转移和复发。我们的研究为增强肿瘤免疫治疗和抑制肿瘤复发和转移提供了新的方法。
    Tumor vaccines have become a promising approach for cancer treatment by triggering antigen-specific responses against tumors. However, autophagy and immunosuppressive tumor microenvironment (TME) reduce antigen exposure and immunogenicity, which limit the effect of tumor vaccines. Here, we develop fucoidan (Fuc) based chlorin e6 (Ce6)-chloroquine (CQ) self-assembly hydrogels (CCFG) as in situ vaccines. Ce6 triggers immune response in situ by photodynamic therapy (PDT) induced immunogenic cell death (ICD) effect, which is further enhanced by macrophage polarization of Fuc and autophagy inhibition of CQ. In vivo studies show that CCFG effectively enhances antigen presentation under laser irradiation, which induces a powerful in situ vaccine effect and significantly inhibits tumor metastasis and recurrence. Our study provides a novel approach for enhancing tumor immunotherapy and inhibiting tumor recurrence and metastasis.
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  • 文章类型: Journal Article
    免疫抑制性肿瘤微环境(TME)仍然是肿瘤控制的主要障碍,并导致对免疫检查点阻断(ICB)治疗的次优反应。因此,制定引发TME炎症反应的可行治疗策略可提高ICB疗效.线粒体在炎症调节和肿瘤免疫原性诱导中起重要作用。在这里,我们报告了一类可以概括水性自组装行为的小分子的发现和表征,特异性靶向细胞器(例如,线粒体),并增强肿瘤细胞的免疫原性。机械上,这个纳米组装平台动态地重新连接线粒体,诱导内质网应激,并导致细胞凋亡/凋亡相关的免疫原性细胞死亡。治疗后,压力和死亡的肿瘤细胞可以作为预防性或治疗性癌症疫苗。在对PD-1阻断具有内在或获得性抗性的癌症的临床前小鼠模型中,纳米组件的局部给药使免疫沉默的TME发炎,并与ICB疗法协同作用,产生有效的抗肿瘤免疫力。这种化学编程的小分子免疫增强剂与常规的细胞毒性疗法明显起作用,并为先天免疫的同步和动态定制提供了有希望的策略,以实现无痕迹的癌症治疗并克服癌症中的免疫抑制。
    The immunosuppressive tumor microenvironment (TME) remains a major obstacle to tumor control and causes suboptimal responses to immune checkpoint blockade (ICB) therapy. Thus, developing feasible therapeutic strategies that trigger inflammatory responses in the TME could improve the ICB efficacy. Mitochondria play an essential role in inflammation regulation and tumor immunogenicity induction. Herein, we report the discovery and characterization of a class of small molecules that can recapitulate aqueous self-assembly behavior, specifically target cellular organelles (e.g., mitochondria), and invigorate tumor cell immunogenicity. Mechanistically, this nanoassembly platform dynamically rewires mitochondria, induces endoplasmic reticulum stress, and causes apoptosis/paraptosis-associated immunogenic cell death. After treatment, stressed and dying tumor cells can act as prophylactic or therapeutic cancer vaccines. In preclinical mouse models of cancers with intrinsic or acquired resistance to PD-1 blockade, the local administration of nanoassemblies inflames the immunologically silent TME and synergizes with ICB therapy, generating potent antitumor immunity. This chemically programmed small-molecule immune enhancer acts distinctly from regular cytotoxic therapeutics and offers a promising strategy for synchronous and dynamic tailoring of innate immunity to achieve traceless cancer therapy and overcome immunosuppression in cancers.
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  • 文章类型: Journal Article
    临床上用于治疗癌症的疫苗的治疗功效仍然有限。这里,报道了通过将免疫原性差异和临床批准的铝(Al)或锰(Mn)与抗原一起置于2D纳米片(NS)结构中而合理设计的癌症疫苗。具有高摩尔比的Mn与Al(MANS-H)的结构最佳NS具有独特的免疫调节,显着促进注射部位异质先天免疫细胞的流入。刺激多个亚群的树突状细胞(DC)显着增加的水平,亚型,和抗原特异性T细胞的功能。通过引发T辅助(Th)2细胞而不是T滤泡辅助(Tfh)细胞,MANS-H在产生抗原特异性抗体方面比商业佐剂(Alhydrogel)更有效。除了体液免疫,MANS-H引起高频率的抗原特异性Th1和CD8+细胞免疫,与广泛用于兽医疫苗的Quil-A相当。具有MANS-H佐剂化疫苗的免疫小鼠通过促进效应T细胞在肿瘤处浸润并克服多种高度侵袭性肿瘤模型中的肿瘤抗性而在肿瘤消退中发挥强效力。具有有趣的NS结构和安全的免疫增强剂的工程免疫原为癌症免疫疗法提供了下一个临床进展。
    The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al) or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS-H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen-specific T cells. MANS-H demonstrates even greater effectiveness in the production of antigen-specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS-H evokes high frequencies of antigen-specific Th1 and CD8+ cell immunity, which are comparable with Quil-A that is widely used in veterinary vaccines. Immunized mice with MANS-H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy.
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  • 文章类型: Journal Article
    背景:胶质瘤,特别是多形性胶质母细胞瘤(GBM),是高度侵袭性的脑肿瘤,由于其快速进展和对常规疗法的抵抗力,在肿瘤学中提出了重大挑战。尽管在治疗方面取得了进展,GBM患者的预后仍然很差,有必要探索新的治疗方法。其中一个新兴战略是神经胶质瘤疫苗的开发,其目的是刺激免疫系统靶向和破坏肿瘤细胞。
    目的:这篇综述旨在对神经胶质瘤疫苗开发的现状进行全面评估,分析正在调查的疫苗类型,临床试验的结果,以及与实施相关的挑战和机遇。目标是强调神经胶质瘤疫苗在为神经胶质瘤患者提供更有效和个性化治疗方面的潜力。
    方法:这篇叙述性综述通过包括2000年至2024年之间以英文发表的全文文章,系统地评估了神经胶质瘤疫苗的作用。数据库,如PubMed/MEDLINE,EMBASE,Cochrane图书馆,和Scopus使用像“神经胶质瘤”这样的关键术语进行搜索,“脑瘤”,胶质母细胞瘤,\"\"疫苗,“和”免疫疗法。“这项审查纳入了临床前和临床研究,包括描述性研究,动物模型研究,队列研究,和观察性研究。排除标准被应用于省略摘要,病例报告,海报,和非同行评审的研究,确保纳入高质量的证据。
    结果:研究各种神经胶质瘤疫苗的临床试验,包括基于肽的,基于DNA/RNA,全细胞,和树突状细胞疫苗,已经显示出有希望的结果。这些疫苗显示出在神经胶质瘤患者中延长存活率和管理不良事件的潜力。然而,重大挑战依然存在,如由于肿瘤异质性和免疫逃避机制引起的治疗抗性。此外,缺乏评估疫苗反应的标准化指南以及与道德考虑相关的问题,监管障碍,以及患者对疫苗的接受进一步使胶质瘤疫苗的实施复杂化。
    结论:解决与神经胶质瘤疫苗相关的挑战包括探索联合疗法,有针对性的方法,个性化医疗。将疫苗与放疗或化疗等传统疗法相结合,可以通过增强免疫系统对抗肿瘤细胞的能力来提高疗效。针对个体患者概况定制的个性化疫苗提供了改善结果的机会。此外,全球合作和公平分配对于确保获得神经胶质瘤疫苗至关重要,特别是在医疗保健资源有限的低收入和中等收入国家。结论:胶质瘤疫苗代表了对抗胶质瘤的一个有希望的途径。为改善众所周知难以治疗的疾病的患者预后提供了希望。尽管面临挑战,继续研究和制定创新战略,包括联合疗法和个性化方法,对于克服目前的障碍和改变神经胶质瘤患者的治疗前景至关重要。
    BACKGROUND: Gliomas, particularly glioblastoma multiforme (GBM), are highly aggressive brain tumors that present significant challenges in oncology due to their rapid progression and resistance to conventional therapies. Despite advancements in treatment, the prognosis for patients with GBM remains poor, necessitating the exploration of novel therapeutic approaches. One such emerging strategy is the development of glioma vaccines, which aim to stimulate the immune system to target and destroy tumor cells.
    OBJECTIVE: This review aims to provide a comprehensive evaluation of the current landscape of glioma vaccine development, analyzing the types of vaccines under investigation, the outcomes of clinical trials, and the challenges and opportunities associated with their implementation. The goal is to highlight the potential of glioma vaccines in advancing more effective and personalized treatments for glioma patients.
    METHODS: This narrative review systematically assessed the role of glioma vaccines by including full-text articles published between 2000 and 2024 in English. Databases such as PubMed/MEDLINE, EMBASE, the Cochrane Library, and Scopus were searched using key terms like \"glioma,\" \"brain tumor,\" \"glioblastoma,\" \"vaccine,\" and \"immunotherapy.\" The review incorporated both pre-clinical and clinical studies, including descriptive studies, animal-model studies, cohort studies, and observational studies. Exclusion criteria were applied to omit abstracts, case reports, posters, and non-peer-reviewed studies, ensuring the inclusion of high-quality evidence.
    RESULTS: Clinical trials investigating various glioma vaccines, including peptide-based, DNA/RNA-based, whole-cell, and dendritic-cell vaccines, have shown promising results. These vaccines demonstrated potential in extending survival rates and managing adverse events in glioma patients. However, significant challenges remain, such as therapeutic resistance due to tumor heterogeneity and immune evasion mechanisms. Moreover, the lack of standardized guidelines for evaluating vaccine responses and issues related to ethical considerations, regulatory hurdles, and vaccine acceptance among patients further complicate the implementation of glioma vaccines.
    CONCLUSIONS: Addressing the challenges associated with glioma vaccines involves exploring combination therapies, targeted approaches, and personalized medicine. Combining vaccines with traditional therapies like radiotherapy or chemotherapy may enhance efficacy by boosting the immune system\'s ability to fight tumor cells. Personalized vaccines tailored to individual patient profiles present an opportunity for improved outcomes. Furthermore, global collaboration and equitable distribution are critical for ensuring access to glioma vaccines, especially in low- and middle-income countries with limited healthcare resources CONCLUSION: Glioma vaccines represent a promising avenue in the fight against gliomas, offering hope for improving patient outcomes in a disease that is notoriously difficult to treat. Despite the challenges, continued research and the development of innovative strategies, including combination therapies and personalized approaches, are essential for overcoming current barriers and transforming the treatment landscape for glioma patients.
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  • 文章类型: Journal Article
    背景:靶向激酶是治疗实体肿瘤的潜在策略;然而,针对激酶的疫苗的治疗潜力仍不确定.
    方法:开发了编码Aurora激酶A(AURKA)或细胞周期蛋白依赖性激酶7(CDK7)的腺病毒(Ad)疫苗,并通过包括蛋白质印迹在内的各种方法研究了它们的治疗潜力,流式细胞术,细胞毒性T淋巴细胞测定,和酶联免疫斑点(ELISpot),在小鼠和人源化实体瘤模型中。
    结果:用Ad-AURKA/CDK7联合免疫可有效防止Renca皮下肿瘤生长,RM-1、MC38和Hepa1-6肿瘤模型。在治疗性肿瘤模型中,Ad-AURKA/CDK7治疗阻碍肿瘤生长并增加免疫细胞浸润。Ad-AURKA/CDK7的施用促进树突状细胞亚群的诱导和成熟,并增强多功能CD8+T细胞抗肿瘤免疫。此外,该疫苗通过促进记忆性CD8+T细胞的产生诱导了持久的抗肿瘤作用。CD8+T细胞耗竭的肿瘤恢复强调了这些细胞在观察到的治疗效果中不可或缺的作用。Ad-AURKA/CDK7疫苗的有效功效在肺转移中得到一致证明,原位,和人源化肿瘤模型通过诱导多功能CD8+T细胞抗肿瘤免疫反应。
    结论:我们的研究结果表明,针对AURKA和CDK7双激酶的Ad-AURKA/CDK7疫苗成为治疗实体肿瘤的一种有希望且有效的治疗方法。
    BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.
    METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.
    RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of Ad-AURKA/CDK7 promoted the induction and maturation of dendritic cell subsets and augmented multifunctional CD8+ T-cell antitumor immunity. Furthermore, the vaccine induced a long-lasting antitumor effect by promoting the generation of memory CD8+ T cells. Tumor recovery on CD8+ T-cell depletion underscored the indispensable role of these cells in the observed therapeutic effects. The potent efficacy of the Ad-AURKA/CDK7 vaccine was consistently demonstrated in lung metastasis, orthotopic, and humanized tumor models by inducing multifunctional CD8+ T-cell antitumor immune responses.
    CONCLUSIONS: Our findings illustrate that the Ad-AURKA/CDK7 vaccine targeting dual kinases AURKA and CDK7 emerges as a promising and effective therapeutic approach for the treatment of solid tumors.
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  • 文章类型: Journal Article
    我们以前报道过两项单药I期试验,评估剂量或时间表,编码前列腺酸性磷酸酶(PAP)的DNA疫苗(pTVG-HP),以GM-CSF作为佐剂。这些是PSA复发的患者,放射学非转移性,前列腺癌(PCa)。我们在此报告这些患者的长期安全性和总体生存率。具体来说,22例非转移性患者,去势敏感性PCa(nmCSPC)用pTVG-HP治疗,100-1500微克,17例非转移性去势抵抗性PCa(nmCRPC)患者接受100µgpTVG-HP治疗,并在1年内采用不同的给药方案,并随访5年。在任何一项试验的长期随访中均未检测到可能与疫苗接种有关的不良事件。nmCSPC患者的中位总生存期为12.3y,5/22(23%)在15岁时存活。8/22(36%)死于前列腺癌,中位生存期为11.0岁,9/22(41%)死于其他原因。nmCRPC患者的中位总生存期为4.5y,8/17(47%)在5年存活。在6/10(60%)患有nmCSPC的个体中可检测到PAP靶抗原特异性的T细胞的存在,和3/5(60%)的nmCRPC个体,免疫接种多年后。免疫后数年对疫苗靶标的免疫应答的检测表明,使用编码肿瘤相关抗原的DNA疫苗可以在患者中引发持久的免疫。试验注册:NCT00582140和NCT00849121。
    We have previously reported two single-agent phase I trials, evaluating the dose or schedule, of a DNA vaccine (pTVG-HP) encoding prostatic acid phosphatase (PAP) administered with GM-CSF as the adjuvant. These were in patients with PSA-recurrent, radiographically non-metastatic, prostate cancer (PCa). We report here the long-term safety and overall survival of these patients. Specifically, 22 patients with non-metastatic, castration-sensitive PCa (nmCSPC) were treated with pTVG-HP, 100-1500 µg, administered over 12 weeks and followed for 15 y. 17 patients with non-metastatic castration-resistant PCa (nmCRPC) were treated with 100 µg pTVG-HP with different schedules of administration over 1 y and followed for 5 y. No adverse events were detected in long-term follow-up from either trial that were deemed possibly related to vaccination. Patients with nmCSPC had a median overall survival of 12.3 y, with 5/22 (23%) alive at 15 y. 8/22 (36%) died due to prostate cancer with a median survival of 11.0 y, and 9/22 (41%) died of other causes. Patients with nmCRPC had a median overall survival of 4.5 y, with 8/17 (47%) alive at 5 y. The presence of T-cells specific for the PAP target antigen was detectable in 6/10 (60%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in patients using a DNA vaccine encoding a tumor-associated antigen.Trial Registration: NCT00582140 and NCT00849121.
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  • 文章类型: Journal Article
    随着COVID-19大流行,疫苗的重要性已得到广泛认可,并导致研究和开发努力增加。疫苗通过激活免疫系统靶向和破坏癌细胞,在癌症治疗中也起着至关重要的作用。然而,提高癌症疫苗的功效仍然是一个挑战。佐剂,增强对抗原的免疫反应并提高疫苗的有效性,近年来面临着局限性,导致很少的新佐剂被鉴定。人工智能(AI)技术在药物开发中的进步为佐剂筛选和应用提供了基础,导致佐剂的多样化。本文综述了肿瘤疫苗在基础研究和临床治疗中的重要作用,并探讨了使用AI技术从数据库中筛选新型佐剂的方法。这篇综述的发现为下一代疫苗新佐剂的开发提供了有价值的见解。
    With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines.
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  • 文章类型: Journal Article
    癌症免疫疗法激活宿主免疫系统对抗肿瘤细胞,并有可能导致癌症治疗创新策略的发展。新抗原是由肿瘤细胞中的遗传突变产生的非自身抗原,其诱导针对肿瘤细胞的强免疫应答而没有中枢免疫耐受。随着新抗原分析技术的进步,专注于新抗原的疫苗的开发正在加速。尽管新抗原疫苗有各种平台,与合成长肽和mRNA以及基于树突细胞(DC)的疫苗的临床应用同时开发了联合免疫疗法。个性化的基于DC的疫苗不仅可以装载包括新抗原在内的各种抗原,但也有可能在T细胞作为抗原呈递细胞引起强烈的免疫反应。在这次审查中,我们描述了新抗原的特性和DC的基本特征。我们还讨论了新抗原疫苗的临床应用,专注于个性化的DC疫苗,以及未来的研发方向和挑战。
    Cancer immunotherapy activates the host immune system against tumor cells and has the potential to lead to the development of innovative strategies for cancer treatment. Neoantigens are non-self-antigens produced by genetic mutations in tumor cells that induce a strong immune response against tumor cells without central immune tolerance. Along with advances in neoantigen analysis technology, the development of vaccines focusing on neoantigens is being accelerated. Whereas there are various platforms for neoantigen vaccines, combined immuno-therapies are being developed simultaneously with the clinical application of synthetic long peptides and mRNA and dendritic-cell (DC)-based vaccines. Personalized DC-based vaccines not only can load various antigens including neoantigens, but also have the potential to elicit a strong immune response in T cells as antigen-presenting cells. In this review, we describe the properties of neoantigens and the basic characteristics of DCs. We also discuss the clinical applications of neoantigen vaccines, focusing on personalized DC-based vaccines, as well as future research and development directions and challenges.
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  • 文章类型: Journal Article
    在这项研究中,从ICD的角度挖掘了mRNA疫苗的有效抗原,和PRAD的ICD亚型进一步区分以建立ICD景观,从而确定合适的疫苗接受者。
    TCGA和MSKCC数据库用于获取554和131名患者的RNA-seq数据和相应的临床数据,分别。采用GEPIA来测量预后指标。然后利用cBioPortal进行遗传改变的比较,使用TIMER分析已鉴定的ICD抗原与免疫浸润细胞的相关性。此外,ICD亚型通过共识聚类鉴定,利用基于图形学习的降维技术描绘了PRAD的ICD景观。
    总共,在PRAD中鉴定了4种PRAD抗原,包括FUS,LMNB2,RNPC3和ZNF700与APCs的不良预后和浸润有关。PRAD患者根据其分子差异分为两种ICD亚型,细胞和临床特征。此外,ICD调节剂和免疫检查点也在两种ICD亚型肿瘤之间差异表达。最后,PRAD的ICD景观在个体患者之间显示出实质性的异质性。
    总之,该研究可能为开发针对PRAD的mRNA疫苗以及确定合适的疫苗接受者提供理论基础。
    UNASSIGNED: In this study, effective antigens of mRNA vaccine were excavated from the perspective of ICD, and ICD subtypes of PRAD were further distinguished to establish an ICD landscape, thereby determining suitable vaccine recipients.
    UNASSIGNED: TCGA and MSKCC databases were applied to acquire RNA-seq data and corresponding clinical data of 554 and 131 patients, respectively. GEPIA was employed to measure prognostic indices. Then, a comparison of genetic alterations was performed utilizing cBioPortal, and correlation of identified ICD antigens with immune infiltrating cells was analyzed employing TIMER. Moreover, ICD subtypes were identified by means of consensus cluster, and ICD landscape of PRAD was depicted utilizing graph learning-based dimensional reduction.
    UNASSIGNED: In total, 4 PRAD antigens were identified in PRAD, including FUS, LMNB2, RNPC3, and ZNF700, which had association with adverse prognosis and infiltration of APCs. PRAD patients were classified as two ICD subtypes based on their differences in molecular, cellular, and clinical features. Furthermore, ICD modulators and immune checkpoints were also differentially expressed between two ICD subtype tumors. Finally, the ICD landscape of PRAD showed substantial heterogeneity among individual patients.
    UNASSIGNED: In summary, the research may provide a theoretical foundation for developing mRNA vaccine against PRAD as well as determining appropriate vaccine recipients.
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