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

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.

Automated summary

Neoantigen provides a promising breakthrough in tumor immunotherapy, and this study developed a pipeline to predict neoantigens based on somatic mutations and gene-expression profiles. The study also constructed a neoantigen immune response score (NAIRscore) integrating neoantigen load, cytolytic score, and HLA-I score, which showed competitive advantage in stratifying multiple myeloma samples and predicting overall survival.