{"title":"The role of neoantigens and tumor mutational burden in cancer immunotherapy: advances, mechanisms, and perspectives","authors":"Shengbo Sun, Lanchun Liu, Jingkang Zhang, Liting Sun, Wenlong Shu, Zhengyang Yang, Hongwei Yao, Zhongtao Zhang","doi":"10.1186/s13045-025-01732-z","DOIUrl":null,"url":null,"abstract":"Cancer immunotherapy has revolutionized oncology by leveraging the immune system to combat tumors. Among various biomarkers, neoantigens and tumor mutational burden (TMB) have emerged as critical factors in tailoring personalized treatments. Neoantigens are tumor-specific peptides displayed on cancer cell surfaces, derived from somatic mutations. Recognized as \"non-self\" by the immune system, they trigger T-cell responses and enable therapies like personalized vaccines and adoptive T-cell transfer. Critically, neoantigen potential correlates with TMB, which quantifies the total somatic mutations within a tumor genome. A higher TMB generally correlates with a greater likelihood of generating immunogenic neoantigens, making it a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI). Progress in high-throughput sequencing, bioinformatics, and immuno-peptidomics has significantly enhanced the accuracy of neoantigen prediction, including assessments of major histocompatibility complex (MHC) binding affinity and T-cell receptor recognition. Clinically, neoantigen-based therapies have shown efficacy in early trials, with strategies such as mRNA vaccines demonstrating synergy with ICI by boosting T-cell activation and overcoming immune suppression. Combining neoantigen-based therapies with chemotherapy and radiotherapy harnesses synergistic mechanisms to enhance efficacy, overcome resistance, and emerge as a pivotal oncology research focus. The integration of TMB into clinical practice has received regulatory approval as a biomarker for stratifying patients for ICI therapies. Furthermore, advanced methodologies like liquid biopsy and single-cell technologies have streamlined TMB measurement, improving its predictive value for personalized immunotherapy. Collectively, neoantigens and TMB have optimized the evolution of precision immuno-oncology by providing frameworks that maximize therapeutic efficacy, overcome resistance mechanisms, and advance durable cancer remission.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"31 1","pages":""},"PeriodicalIF":40.4000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13045-025-01732-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cancer immunotherapy has revolutionized oncology by leveraging the immune system to combat tumors. Among various biomarkers, neoantigens and tumor mutational burden (TMB) have emerged as critical factors in tailoring personalized treatments. Neoantigens are tumor-specific peptides displayed on cancer cell surfaces, derived from somatic mutations. Recognized as "non-self" by the immune system, they trigger T-cell responses and enable therapies like personalized vaccines and adoptive T-cell transfer. Critically, neoantigen potential correlates with TMB, which quantifies the total somatic mutations within a tumor genome. A higher TMB generally correlates with a greater likelihood of generating immunogenic neoantigens, making it a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI). Progress in high-throughput sequencing, bioinformatics, and immuno-peptidomics has significantly enhanced the accuracy of neoantigen prediction, including assessments of major histocompatibility complex (MHC) binding affinity and T-cell receptor recognition. Clinically, neoantigen-based therapies have shown efficacy in early trials, with strategies such as mRNA vaccines demonstrating synergy with ICI by boosting T-cell activation and overcoming immune suppression. Combining neoantigen-based therapies with chemotherapy and radiotherapy harnesses synergistic mechanisms to enhance efficacy, overcome resistance, and emerge as a pivotal oncology research focus. The integration of TMB into clinical practice has received regulatory approval as a biomarker for stratifying patients for ICI therapies. Furthermore, advanced methodologies like liquid biopsy and single-cell technologies have streamlined TMB measurement, improving its predictive value for personalized immunotherapy. Collectively, neoantigens and TMB have optimized the evolution of precision immuno-oncology by providing frameworks that maximize therapeutic efficacy, overcome resistance mechanisms, and advance durable cancer remission.
期刊介绍:
The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts.
Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.