NAIRscore as a biomarker for the quality of immune response to neoantigens is related with an increased overall survival in multiple myeloma

Xingxing Jian; Linfeng Xu; Jingjing Zhao; Yanhui Wang; Wen Zhou; Lu Xie

Molecular Therapy: Nucleic Acids (Sep 2022)

NAIRscore as a biomarker for the quality of immune response to neoantigens is related with an increased overall survival in multiple myeloma

Xingxing Jian,
Linfeng Xu,
Jingjing Zhao,
Yanhui Wang,
Wen Zhou,
Lu Xie

Affiliations

Xingxing Jian: Bioinformatics Center & National Clinical Research Centre for Geriatric Disorders & Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Corresponding author Xingxing Jian, Bioinformatics Center, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Linfeng Xu: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Institute for Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China; School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
Jingjing Zhao: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Institute for Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China; College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
Yanhui Wang: College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
Wen Zhou: Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Lu Xie: Bioinformatics Center & National Clinical Research Centre for Geriatric Disorders & Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Institute for Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China; Corresponding author Lu Xie, Bioinformatics Center, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Journal volume & issue: Vol. 29
pp. 285 – 295

Abstract

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Neoantigen provides a promising breakthrough in tumor immunotherapy, although only a subset of patients responds well due to the quality of their immune response. However, few biomarkers have been reported to measure the quality of immune response to neoantigens and to predict prognosis of patients with multiple myeloma (MM). Here, we first developed a neoantigen-prediction pipeline starting from outcomes of somatic mutations and gene-expression profiles. Given the expression of some specific marker genes, the human leukocyte antigen (HLA)-I score and the cytolytic score were evaluated respectively to reflect HLA-I molecular expression and CD8+ T/natural killer (NK) cell abundance. According to the process of the immune response to neoantigens, we comprehensively took neoantigen load, cytolytic score, and HLA-I score to construct a neoantigen immune response score (NAIRscore), in which the HLA-I score presented a hazard ratio (HR) of less than 1, while the cytolytic score and neoantigen load presented a HR of greater than 1. Meanwhile, NAIRscore presented a competitive advantage to stratify MM samples. Especially, those exhibiting high NAIRscore correlated with an increased overall survival (OS), echoing the underlying molecular signatures of lower driver-gene mutations and down-regulated immune response. Notably, an online tool based on this study is provided to identify neoantigens and predict OS.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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