Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine

Molecular Cancer

Hang Xu¹  Qiang Wei¹  Tianyi Zhang¹  Hong Li¹  Xianyanling Yi¹  Jianzhong Ai¹  Xiaonan Zheng² 

[1] Institute of Urology, West China Hospital, Sichuan University, 610041, Chengdu, China;Department of Urology, West China Hospital, Sichuan University, 610041, Chengdu, China;Institute of Urology, West China Hospital, Sichuan University, 610041, Chengdu, China;Department of Urology, West China Hospital, Sichuan University, 610041, Chengdu, China;Institute of Systems Genetics, West China Hospital, Sichuan University, 610041, Chengdu, China;

关键词: mRNA vaccine;    Prostate adenocarcinoma;    Immunotherapy;    Tumor antigens;    Immune subtypes;    Immune landscape;   

DOI  :  10.1186/s12943-021-01452-1

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY