Based on the identification of tumor antigens and immune subtypes in renal clear cell carcinoma for mRNA vaccine development
Based on the identification of tumor antigens and immune subtypes in renal clear cell carcinoma for mRNA vaccine development
Abstract BackgroundCancer vaccine based on mRNA is considered as a promising strategy and has become a new hot spot in cancer immunotherapy. However, its application to KIRC is not clear. A growing body of research has shown that immunotyping can reflect the comprehensive immune status and immune microenvironment of tumor, which is closely related to treatment response and vaccination potential. The aim of this study was to identify the potential antigens of KIRC for the development of anti-KIRC mRNA vaccines, and to further differentiate the immune subtypes of KIRC to construct an immune landscape for the selection of appropriate patients for vaccination. MethodsGene expression profiles and corresponding clinical information of 265 KIRC patients and RNA-seq data of 539 KIRC patients were retrieved from were collected from GEO and TCGA. cBioPortal was used to visualize and compare genetic alterations, while GEPIA2 was used to calculate the prognostic index of selected antigens. The relationship between the infiltration of antigen presenting cells and the expression of the identified antigen was visualized with TIMER, and consensus clustering analysis was used to determine the immune subtypes. Finally, the immune landscape of KIRC is visualized through the dimensionality reduction analysis based on graph learning. ResultsTwo tumor antigens associated with prognostic and antigen-presenting infiltrating cells were identified in KIRC, including LRP2, and DOCK8. KIRC patients were classified into six immune subtypes based on different molecular, cellular, and clinical characteristics. Patients with IS5 and IS6 tumors had an immune “hot” and immunosuppressive phenotype, which was associated with better survival compared to other subtypes, whereas patients with IS1-4 tumors had an immune “cold” phenotype, which was associated with a higher tumor mutation burden. In addition, the expression of immune checkpoints and immunogenic cell death modulators differed significantly in different immunosubtypes of tumors. Finally, the immune landscape of KIRC shows a high degree of heterogeneity across patients. ConclusionsLRP2 and FEM2 are potential KIRC antigens for mRNA vaccine development, and patients with immune subtypes IS1-4 are suitable for vaccination.
Xiong Yu、Ouyang Yan、Mao Chengju、Zhang Shichao、Kang Shijing、Peng Jian、Zeng Zhu、Wang Yue
Key Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical UniversityKey Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical UniversityThe Key and Characteristic Laboratory of Modern Pathogen Biology, Basic Medical College, Guizhou Medical UniversityKey Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical UniversityKey Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical UniversityKey Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical University||Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University||The Key and Characteristic Laboratory of Modern Pathogen Biology, Basic Medical College, Guizhou Medical UniversityKey Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical University||Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical UniversityKey Laboratory of Infection Immunity and Antibody Engineering of Guizhou Province, School of Biology and Engineering & School of Basic Medical Sciences, Guizhou Medical University||The Key and Characteristic Laboratory of Modern Pathogen Biology, Basic Medical College, Guizhou Medical University
肿瘤学医学研究方法基础医学
mRNA vaccineKidney renal clear cell carcinomaTumor antigensImmune subtypesImmune landscape
Xiong Yu,Ouyang Yan,Mao Chengju,Zhang Shichao,Kang Shijing,Peng Jian,Zeng Zhu,Wang Yue.Based on the identification of tumor antigens and immune subtypes in renal clear cell carcinoma for mRNA vaccine development[EB/OL].(2025-03-28)[2025-05-06].https://www.biorxiv.org/content/10.1101/2021.07.04.451033.点此复制
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