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Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine
Molecular Cancer ( IF 27.7 ) Pub Date : 2021-12-06 , DOI: 10.1186/s12943-021-01452-1
Xiaonan Zheng 1, 2, 3 , Hang Xu 1, 2 , Xianyanling Yi 1, 2 , Tianyi Zhang 1, 2 , Qiang Wei 1, 2 , Hong Li 1, 2 , Jianzhong Ai 1, 2
Affiliation  

Prostate adenocarcinoma (PRAD) is a leading cause of death among men. Messenger ribonucleic acid (mRNA) vaccine presents an attractive approach to achieve satisfactory outcomes; however, tumor antigen screening and vaccination candidates show a bottleneck in this field. We aimed to investigate the tumor antigens for mRNA vaccine development and immune subtypes for choosing appropriate patients for vaccination. We identified eight overexpressed and mutated tumor antigens with poor prognostic value of PRAD, including KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The correlation of those genes with antigen-presenting immune cells were assessed. We further identified three immune subtypes of PRAD (PRAD immune subtype [PIS] 1–3) with distinct clinical, molecular, and cellular characteristics. PIS1 showed better survival and immune cell infiltration, nevertheless, PIS2 and PIS3 showed cold tumor features with poorer prognosis and higher tumor genomic instability. Moreover, these immune subtypes presented distinguished association with immune checkpoints, immunogenic cell death modulators, and prognostic factors of PRAD. Furthermore, immune landscape characterization unraveled the immune heterogeneity among patients with PRAD. To summarize, our study suggests KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3 are potential antigens for PRAD mRNA vaccine development, and patients in the PIS2 and PIS3 groups are more suitable for vaccination.

中文翻译:


前列腺癌 mRNA 疫苗的肿瘤抗原和免疫景观鉴定



前列腺腺癌(PRAD)是男性死亡的主要原因。信使核糖核酸 (mRNA) 疫苗提供了一种实现令人满意的结果的有吸引力的方法;然而,肿瘤抗原筛选和候选疫苗接种显示出该领域的瓶颈。我们的目的是研究用于 mRNA 疫苗开发的肿瘤抗原和免疫亚型,以选择合适的患者进行疫苗接种。我们鉴定了 8 种 PRAD 预后价值较差的过表达和突变肿瘤抗原,包括 KLHL17、CPT1B、IQGAP3、LIME1、YJEFN3、KIAA1529、MSH5 和 CELSR3。评估了这些基因与抗原呈递免疫细胞的相关性。我们进一步鉴定了具有不同临床、分子和细胞特征的三种 PRAD 免疫亚型(PRAD 免疫亚型 [PIS] 1-3)。 PIS1表现出更好的存活率和免疫细胞浸润,然而,PIS2和PIS3表现出冷肿瘤特征,预后较差,肿瘤基因组不稳定性较高。此外,这些免疫亚型与免疫检查点、免疫原性细胞死亡调节剂和 PRAD 预后因素存在显着关联。此外,免疫景观特征揭示了 PRAD 患者的免疫异质性。综上所述,我们的研究表明KLHL17、CPT1B、IQGAP3、LIME1、YJEFN3、KIAA1529、MSH5和CELSR3是PRAD mRNA疫苗开发的潜在抗原,PIS2和PIS3组的患者更适合接种疫苗。
更新日期:2021-12-06
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