TY - JOUR
T1 - ImmunoMap
T2 - A bioinformatics tool for T-cell repertoire analysis
AU - Sidhom, John William
AU - Bessell, Catherine A.
AU - Havel, Jonathan J.
AU - Kosmides, Alyssa
AU - Chan, Timothy A.
AU - Schneck, Jonathan P.
N1 - Funding Information:
NIH (R01-AI44129, CA108835, and U01 – AI113315). Animal and clinical protocol images were reproduced under a Creative Commons License from Servier Medical Art (http://www.servier.com/Powerpoint-image-bank). This work was funded by Bristol Myers-Squibb, the Pershing Square Sohn Cancer Research Foundation (T.A. Chan), the PaineWebber Chair (T.A. Chan), Stand Up To Cancer (T.A. Chan), and the STARR Cancer Consortium (T.A. Chan). Partial Support was provided by the MSK Core Grant (P30 CA008748). Research supported by a Stand Up To Cancer - American Cancer Society Lung Cancer Dream Team Translational Research Grant (Grant Number: SU2C-AACR-DT17-15). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C.
Funding Information:
The authors thank the JHU-Coulter Translational Partnership, the TEDCO Maryland Innovation Initiative, The Troper Wojcicki Foundation, and the NIH (R01-AI44129, CA108835, and U01-AI113315).
Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/2
Y1 - 2018/2
N2 - 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- A nd posttherapy samples.
AB - 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- A nd posttherapy samples.
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U2 - 10.1158/2326-6066.CIR-17-0114
DO - 10.1158/2326-6066.CIR-17-0114
M3 - Article
C2 - 29263161
AN - SCOPUS:85041929177
SN - 2326-6066
VL - 6
SP - 151
EP - 162
JO - Cancer immunology research
JF - Cancer immunology research
IS - 2
ER -