Zhang Shichao, Xia Kaide, Chang Yue, Wei Yimei, Xiong Yu, Tang Fuzhou, Peng Jian, Ouyang Yan
Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China.
Clinical College of Maternal and Child Health Care, Guizhou Medical University, Guiyang 550025, China.
Vaccines (Basel). 2023 Feb 9;11(2):396. doi: 10.3390/vaccines11020396.
The administration of mRNA-based tumour vaccines is considered a promising strategy in tumour immunotherapy, although its application against kidney renal clear cell carcinoma (KIRC) is still at its infancy stage. The purpose of this study was to identify potential antigens and to further select suitable patients for vaccination. Gene expression data and clinical information were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. GEPIA2 was used to evaluate the prognostic value of selected antigens. The relationship of antigens presenting cell infiltration with antigen expression was evaluated by TIMER, and immune subtypes were determined using unsupervised cluster analysis. Tumour antigens LRP2 and DOCK8, which are associated with prognosis and tumour-infiltrating antigen-presenting cells, were identified in KIRC. A total of six immune subtypes were identified, and patients with immune subtype 1-4 (IS1-4) tumours had an immune 'cold' phenotype, a higher tumour mutation burden, and poor survival. Moreover, these immune subtypes showed significant differences in the expression of immune checkpoint and immunogenic cell death modulators. Finally, the immune landscape of KIRC revealed the immune-related cell components in individual patients. This study suggests that LRP2 and DOCK8 are potential KIRC antigens in the development of mRNA vaccines, and patients with immune subtypes IS1-4 are suitable for vaccination.
基于mRNA的肿瘤疫苗给药被认为是肿瘤免疫治疗中一种有前景的策略,尽管其在肾透明细胞癌(KIRC)中的应用仍处于起步阶段。本研究的目的是识别潜在抗原,并进一步筛选适合接种疫苗的患者。从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库中检索基因表达数据和临床信息。使用GEPIA2评估所选抗原的预后价值。通过TIMER评估抗原呈递细胞浸润与抗原表达的关系,并使用无监督聚类分析确定免疫亚型。在KIRC中鉴定出与预后和肿瘤浸润抗原呈递细胞相关的肿瘤抗原LRP2和DOCK8。共鉴定出六种免疫亚型,免疫亚型1-4(IS1-4)肿瘤患者具有免疫“冷”表型、较高的肿瘤突变负荷和较差的生存率。此外,这些免疫亚型在免疫检查点和免疫原性细胞死亡调节剂的表达上存在显著差异。最后,KIRC的免疫图谱揭示了个体患者中与免疫相关的细胞成分。本研究表明,LRP2和DOCK8是mRNA疫苗开发中潜在的KIRC抗原,免疫亚型IS1-4的患者适合接种疫苗。
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