The role of neoantigens and tumor mutational burden in cancer immunotherapy: advances, mechanisms, and perspectives

🥇 Top 1% JournalSep 2, 2025Journal of hematology & oncology

How new tumor markers and mutation levels relate to cancer immunotherapy: progress, mechanisms, and future directions

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Abstract

, derived from somatic mutations, are associated with (TMB) as critical factors in personalizing cancer immunotherapy.

Neoantigens are specific peptides from cancer mutations that can trigger immune responses.
Higher TMB is generally correlated with an increased chance of producing immunogenic neoantigens.
TMB serves as a predictive biomarker for the effectiveness of immune checkpoint inhibitors (ICI).
Advancements in sequencing and bioinformatics have improved the prediction of neoantigens and their interactions with the immune system.
Early clinical trials indicate that neoantigen-based therapies, such as mRNA vaccines, can enhance T-cell activation when used with ICI.
Integration of TMB into clinical practice has been approved for stratifying patients for ICI therapies.

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Cancer immunotherapy has revolutionized oncology by leveraging the immune system to combat tumors. Among various biomarkers, and (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..

Key numbers

44%

Recurrence Risk Reduction

Reduction in recurrence risk compared to alone.

78.6%

18-Month Recurrence-Free Survival Rate

Survival rate for patients treated with the mRNA vaccine plus .

29%

Objective Response Rate

Response rate in -high patients treated with .

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