ImmunoMap: A Bioinformatics Tool for T-cell Repertoire Analysis

被引:33
作者
Sidhom, John-William [1 ,2 ]
Bessell, Catherine A. [3 ,4 ]
Havel, Jonathan J. [5 ,6 ]
Kosmides, Alyssa [1 ,4 ]
Chan, Timothy A. [5 ,6 ]
Schneck, Jonathan P. [4 ,7 ,8 ,9 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Bloomberg Kimmel Inst Canc Immunotherapy, Baltimore, MD USA
[3] Johns Hopkins Univ, Grad Program Immunol, Sch Med, Baltimore, MD USA
[4] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA
[5] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA
[6] Mem Sloan Kettering Canc Ctr, Immunogen & Precis Oncol Platform, 1275 York Ave, New York, NY 10021 USA
[7] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[8] Johns Hopkins Whiting Sch Engn, Inst Nanobiotechnol, Baltimore, MD USA
[9] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
关键词
ANTIGEN-PRESENTING CELLS; ADOPTIVE IMMUNOTHERAPY; METASTATIC MELANOMA; RECEPTOR REPERTOIRE; CENTRAL TOLERANCE; LYMPHOCYTES; DIVERSITY; CANCER; TUMORS; RECONSTITUTION;
D O I
10.1158/2326-6066.CIR-17-0114
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (K-b-TRP2) or to a model foreign antigen (K-b-SIY) in naive 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. (C) 2017 AACR.
引用
收藏
页码:151 / 162
页数:12
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