Improvement in neoantigen prediction via integration of RNA sequencing data for variant calling

Frontiers in Immunology

Immunology

Hoa Giang¹  Bui Que Tran Nguyen¹  Thanh Nhan Nguyen¹  Hoai-Nghia Nguyen¹  Hoang Thien Phuc Nguyen¹  Thi Phuong Diem Tran¹  Vy Nguyen¹  Thi Mong Quynh Pham¹  Le Son Tran¹  Minh-Duy Phan¹  Thanh Sang Tran²  Truong-Vinh Ngoc Pham²  Huu Thinh Nguyen²  Duc Huy Tran²  Minh-Triet Le² 

[1] Medical Genetics Institute, Ho Chi Minh, Vietnam;University Medical Center Ho Chi Minh City, Ho Chi Minh, Vietnam;

关键词: neoantigen;    colorectal cancer (CRC);    RNA sequencing (RNAseq);    tumor variant calling;    neoantigen identification workflow;    Neoantigen prioritization;    cancer immunotherapy;   

DOI  :  10.3389/fimmu.2023.1251603

 received in 2023-07-02, accepted in 2023-08-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionNeoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow.MethodsIn this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP).ResultsWe detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data.DiscussionThis integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients.

【 授权许可】

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Copyright © 2023 Nguyen, Tran, Nguyen, Nguyen, Pham, Nguyen, Tran, Nguyen, Tran, Pham, Le, Phan, Giang, Nguyen and Tran