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Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma
Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from th...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645676/ https://www.ncbi.nlm.nih.gov/pubmed/34872567 http://dx.doi.org/10.1186/s12943-021-01465-w |
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author | Xu, Hang Zheng, Xiaonan Zhang, Shiyu Yi, Xianyanling Zhang, Tianyi Wei, Qiang Li, Hong Ai, Jianzhong |
author_facet | Xu, Hang Zheng, Xiaonan Zhang, Shiyu Yi, Xianyanling Zhang, Tianyi Wei, Qiang Li, Hong Ai, Jianzhong |
author_sort | Xu, Hang |
collection | PubMed |
description | Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-021-01465-w. |
format | Online Article Text |
id | pubmed-8645676 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86456762021-12-06 Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma Xu, Hang Zheng, Xiaonan Zhang, Shiyu Yi, Xianyanling Zhang, Tianyi Wei, Qiang Li, Hong Ai, Jianzhong Mol Cancer Letter to the Editor Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-021-01465-w. BioMed Central 2021-12-06 /pmc/articles/PMC8645676/ /pubmed/34872567 http://dx.doi.org/10.1186/s12943-021-01465-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Letter to the Editor Xu, Hang Zheng, Xiaonan Zhang, Shiyu Yi, Xianyanling Zhang, Tianyi Wei, Qiang Li, Hong Ai, Jianzhong Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
title | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
title_full | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
title_fullStr | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
title_full_unstemmed | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
title_short | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
title_sort | tumor antigens and immune subtypes guided mrna vaccine development for kidney renal clear cell carcinoma |
topic | Letter to the Editor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645676/ https://www.ncbi.nlm.nih.gov/pubmed/34872567 http://dx.doi.org/10.1186/s12943-021-01465-w |
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