Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma.
Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma.
复制标题
鉴定用于发育于免疫性间皮瘤的MRNA疫苗的潜在抗原。
DOI：
10.3389/fcell.2022.879278
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
信使RNA疫苗被认为是一种有前途的策略，在癌症免疫治疗，而他们的应用间皮瘤在很大程度上仍然是不确定的。本研究旨在鉴定间皮瘤中用于抗间皮瘤mRNA疫苗开发的潜在抗原，并进一步确定间皮瘤的免疫亚型，以便从极其异质的人群中选择合适的候选者。基因表达数据和相应的临床病理信息分别从TCGA和基因表达综合数据库获得。然后，使用cBioPortal比较和可视化遗传改变，并通过GEPIA鉴定差异表达的基因及其预后特征。TIMER在线系统评价肿瘤浸润免疫细胞与肿瘤抗原表达的关系。最后，分别采用一致性聚类和基于图学习的降维方法对间皮瘤的免疫亚型和免疫景观进行分析。共鉴定出5种与预后和抗原呈递细胞浸润相关的潜在肿瘤抗原，包括AUNIP、FANCI、LASP 1、PSMD 8和XPO 5。根据免疫相关基因的表达，将间皮瘤患者分为两种免疫亚型（IS1和IS2）。每个亚型表现出不同的分子，细胞和临床特性。IS1亚型患者的特征是免疫“冷”表型，显示出上级生存结局，而IS2亚型患者的特征是免疫“热”和免疫抑制表型。此外，免疫检查点和免疫原性细胞死亡调节剂在IS1和IS2免疫亚型肿瘤之间差异表达。间皮瘤的免疫基因组学景观揭示了个体患者之间复杂的肿瘤免疫微环境。AUNIP、FANCI、LASP1、PSMD8和XPO5是开发抗间皮瘤mRNA疫苗的假定抗原，可考虑对IS 1亚型患者进行疫苗接种。
Messenger RNA vaccines are considered to be a promising strategy in cancer immunotherapy, while their application on mesothelioma is still largely uncharacterized. This study aimed to identify potential antigens in mesothelioma for anti-mesothelioma mRNA vaccine development, and further determine the immune subtypes of mesothelioma for selection of suitable candidates from an extremely heterogeneous population. Gene expression data and corresponding clinicopathological information were obtained from the TCGA and gene expression omnibus, respectively. Then, the genetic alterations were compared and visualized using cBioPortal, and differentially expressed genes and their prognostic signatures were identified by GEPIA. The relationship between tumor-infiltrating immune cells and the expression of tumor antigens was systematically evaluated by TIMER online. Finally, the immune subtypes and immune landscape of mesothelioma were separately analyzed using consensus cluster and graph learning-based dimensional reduction. A total of five potential tumor antigens correlated with prognosis and infiltration of antigen-presenting cells, including AUNIP, FANCI, LASP1, PSMD8, and XPO5 were identified. Based on the expression of immune-related genes, patients with mesothelioma were divided into two immune subtypes (IS1 and IS2). Each subtype exhibited differential molecular, cellular and clinical properties. Patients with the IS1 subtype were characterized by an immune “cold” phenotype, displaying superior survival outcomes, whereas those with the IS2 subtype were characterized by an immune “hot” and immunosuppressive phenotype. Furthermore, immune checkpoints and immunogenic cell death modulators were differentially expressed between the IS1 and IS2 immune subtype tumors. The immunogenomic landscape of mesothelioma revealed a complex tumor immune microenvironment between individual patients. AUNIP, FANCI, LASP1, PSMD8, and XPO5 are putative antigens for the development of anti-mesothelioma mRNA vaccine and patients with the IS1 subtype may be considered for vaccination.