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Cancer Immunol Res. 2018 Feb;6(2):151-162. doi: 10.1158/2326-6066.CIR-17-0114. Epub 2017 Dec 20.

ImmunoMap: A Bioinformatics Tool for T-cell Repertoire Analysis.

Author information

1
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
4
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
5
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
6
Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, New York.
7
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland. jschnec1@jhmi.edu.
8
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
9
Institute for Nanobiotechnology, Johns Hopkins Whiting School of Engineering, Baltimore, Maryland.
10
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

Despite a dramatic increase in T-cell receptor (TCR) sequencing, few approaches biologically parse the data in a fashion that both helps yield new information about immune responses and may guide immunotherapeutic interventions. To address this issue, we developed a method, ImmunoMap, that utilizes a sequence analysis approach inspired by phylogenetics to examine TCR repertoire relatedness. ImmunoMap analysis of the CD8 T-cell response to self-antigen (Kb-TRP2) or to a model foreign antigen (Kb-SIY) in naïve and tumor-bearing B6 mice showed differences in the T-cell repertoire of self- versus foreign antigen-specific responses, potentially reflecting immune pressure by the tumor, and also detected lymphoid organ-specific differences in TCR repertoires. When ImmunoMap was used to analyze clinical trial data of tumor-infiltrating lymphocytes from patients being treated with anti-PD-1, ImmunoMap, but not standard TCR sequence analyses, revealed a clinically predicative signature in pre- and posttherapy samples. Cancer Immunol Res; 6(2); 151-62. ©2017 AACR.

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