The landscape of antigen-specific T cells in human cancers
The landscape of antigen-specific T cells in human cancers
Abstract Antigen-specific T cells can be orchestrated to kill cancer cells in immunotherapies but the utilities of the TCR information have not been fully explored. Here, we leveraged previous efforts on tumor TCR repertoire, and developed a novel algorithm to characterize antigen-specific TCR clusters. Joint analysis with gene expression revealed novel regulators for T cell activation. Investigation of single-cell sequencing data revealed a novel subset of tissue-resident memory T cell population with elevated metabolic status. Integrative analysis of TCR clusters with HLA alleles and cancer genomics data identified candidate antigens derived from missense mutations, frameshift indels, and tumor-associated gene overexpression. Predicted antigen HSFX1 was further validated using vaccinated humanized HLA-A*02:01 mice. Finally, high abundant cancer-associated TCRs were observed in the blood repertoire of early breast cancer patients, suggesting new avenues for noninvasive early detection. Thus, our analysis identified cancer-associated T cells with broad utilities in immune monitoring and cancer immunotherapies.
Filatenkov Alexander、Zhan Xiaowei、Wu Catherine、Li Bo、Zhang Jian、Qiao Jian、Shukla Sachet、Liu Longchao、Chen Jiahui、Ye Jianfeng、Fu Yang-Xin
Department of Pathology, UT Southwestern Medical CenterDepartment of Clinical Science, UT Southwestern Medical CenterMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical SchoolLyda Hill Department of Bioinformatics, UT Southwestern Medical Center||Department of Immunology, UT Southwestern Medical CenterBeijing Institute of Basic Medical SciencesDepartment of Pathology, UT Southwestern Medical CenterMedical Oncology, Dana-Farber Cancer Institute, Harvard Medical SchoolDepartment of Pathology, UT Southwestern Medical CenterLyda Hill Department of Bioinformatics, UT Southwestern Medical CenterLyda Hill Department of Bioinformatics, UT Southwestern Medical CenterDepartment of Pathology, UT Southwestern Medical Center
肿瘤学医学研究方法基础医学
antigen-specific T celltumor-infiltrating T lymphocytesingle-cell sequencingtissue-resident memory signaturecancer-associated antigenhumanized mouseTCR repertoire sequencingnon-invasive cancer diagnosis
Filatenkov Alexander,Zhan Xiaowei,Wu Catherine,Li Bo,Zhang Jian,Qiao Jian,Shukla Sachet,Liu Longchao,Chen Jiahui,Ye Jianfeng,Fu Yang-Xin.The landscape of antigen-specific T cells in human cancers[EB/OL].(2025-03-28)[2025-05-28].https://www.biorxiv.org/content/10.1101/459842.点此复制
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