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The landscape of antigen-specific T cells in human cancers

Bo Li, Longchao Liu, Jian Zhang, Jiahui Chen, Jianfeng Ye, Alexander Filatenkov, Sachet Shukla, Jian Qiao, Xiaowei Zhan, Catherine Wu, Yang-Xin Fu
doi: https://doi.org/10.1101/459842
Bo Li
1Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA
2Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA
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  • For correspondence: bo.li@utsouthwestern.edu
Longchao Liu
3Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
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Jian Zhang
4Beijing Institute of Basic Medical Sciences, Beijing, 100850, China
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Jiahui Chen
1Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA
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Jianfeng Ye
1Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA
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Alexander Filatenkov
3Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
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Sachet Shukla
5Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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Jian Qiao
3Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
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Xiaowei Zhan
6Department of Clinical Science, UT Southwestern Medical Center, Dallas, TX, USA
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Catherine Wu
5Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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Yang-Xin Fu
3Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
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  • For correspondence: bo.li@utsouthwestern.edu
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 01, 2018.
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The landscape of antigen-specific T cells in human cancers
Bo Li, Longchao Liu, Jian Zhang, Jiahui Chen, Jianfeng Ye, Alexander Filatenkov, Sachet Shukla, Jian Qiao, Xiaowei Zhan, Catherine Wu, Yang-Xin Fu
bioRxiv 459842; doi: https://doi.org/10.1101/459842
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The landscape of antigen-specific T cells in human cancers
Bo Li, Longchao Liu, Jian Zhang, Jiahui Chen, Jianfeng Ye, Alexander Filatenkov, Sachet Shukla, Jian Qiao, Xiaowei Zhan, Catherine Wu, Yang-Xin Fu
bioRxiv 459842; doi: https://doi.org/10.1101/459842

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