RT Journal Article
SR Electronic
T1 The landscape of antigen-specific T cells in human cancers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 459842
DO 10.1101/459842
A1 Bo Li
A1 Longchao Liu
A1 Jian Zhang
A1 Jiahui Chen
A1 Jianfeng Ye
A1 Alexander Filatenkov
A1 Sachet Shukla
A1 Jian Qiao
A1 Xiaowei Zhan
A1 Catherine Wu
A1 Yang-Xin Fu
YR 2018
UL http://biorxiv.org/content/early/2018/11/01/459842.abstract
AB 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.