High-throughput sequencing unveils tumor-immune interactions: From genomic alterations to clinical translation

Abstract

High-throughput sequencing (HTS) has revolutionized tumor immunology by enabling precise dissection of tumor-immune interactions, directly informing the development of precision immunotherapies. This review highlights key advances in HTS technologies—including whole genome sequencing (WGS), RNA sequencing, assay for transposase-accessible chromatin using sequencing, and single-cell immunogenomics (scTCR-seq/scBCR-seq)—and their clinical translation in personalized cancer vaccines, engineered T-cell therapies, and combination regimens. We discuss how these tools decode tumor-specific mutations, immune evasion mechanisms, and therapeutic targets, while addressing challenges in data standardization, sample processing, and computational integration. Emerging breakthroughs such as spatial multiomics, real-time monitoring, and artificial intelligence-driven discovery are transforming the field by enabling dynamic, personalized treatment strategies. Finally, we outline future directions to overcome current barriers and expand equitable access to HTS-driven precision immunotherapies.

Keywords

High-throughput sequencing / Tumor immunology / Neoantigen vaccines / Spatial multiomics / Artificial intelligence-driven discovery

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81972713) and the China Postdoctoral Science Foundation (Grant No. PC2018018).

Conflict of interest

Ling Yin is the Guest Editor of this special issue, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly.

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