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Immunotherapy and Immune Responses / Vaccines and Immunoinformatics Approaches · Journal article
Febs Journal · August 12, 2026
Raises a question worth testing. It does not answer one.
This is a narrative review of neoantigen identification modalities and their sources, including whole-exome sequencing, HLA ligandome analysis, and emerging experimental validation platforms. The review summarizes technological advances and identifies open questions about neoantigen-directed immunotherapy, but does not report empirical efficacy data or comparative outcome evidence.
Journal article. Patients with cancer; focus on mechanisms of immune response to neoantigens across tumor types.
Only a subset of patients receiving immune checkpoint inhibitors achieve durable clinical responses, highlighting need for better understanding of antitumor immunity determinants Whole-exome sequencing identifies limited numbers of neoantigens; HLA ligandome analyses have extended neoantigen source landscape to include peptides from noncoding regions Multiple experimental platforms have been developed to validate neoantigen immunogenicity, complemented by single-cell RNA/T-cell receptor sequencing to identify tumor-reactive T cell clones
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This review is intended for researchers and clinicians developing neoantigen-directed cancer vaccines and adoptive cell therapies to understand available identification and validation strategies. However, as a review article without primary evidence or outcome data, it does not provide sufficient evidence to change clinical practice directly.
A narrative review summarizing neoantigen identification strategies and discussing challenges; raises questions about mechanistic pathways rather than reporting empirical results with effect sizes.
This review is intended for researchers and clinicians developing neoantigen-directed cancer vaccines and adoptive cell therapies to understand available identification and validation strategies. However, as a review article without primary evidence or outcome data, it does not provide sufficient evidence to change clinical practice directly.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Immune checkpoint inhibitors (ICIs), which restore antitumor immunity mediated by T cells, have caused a paradigm shift in cancer therapy. However, only a subset of patients achieve durable clinical responses, highlighting the need to better understand the mechanisms that determine antitumor immunity. Cancer-specific neoantigens are considered key determinants of effective immune responses because they are recognized as non-self by T cells and can induce strong immune responses. Accordingly, neoantigens are considered promising targets for cancer vaccines and adoptive cell therapies. Neoantigens have conventionally been considered to arise from somatic mutations and have been identified using whole-exome sequencing (WES). However, the number of neoantigens identified with WES remains limited. In contrast, advances in technology have revealed that peptides derived from various sources, including noncoding regions, are immunogenic and function as neoantigens. In particular, human leukocyte antigen (HLA) ligandome analyses, which enabled the direct identification of peptides presented on HLA molecules in combination with various sequencing technologies, have extended the landscape of neoantigen sources. However, in many cases, the immunogenicity of the identified neoantigen candidates has not been experimentally evaluated. Recently, several experimental platforms have been developed to validate neoantigen immunogenicity, which can be complemented by single-cell RNA/T-cell receptor sequencing to identify tumor-reactive T cell clones. In this review, we summarize current neoantigen identification strategies and discuss the challenges and future perspectives in neoantigen research.
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