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 - 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 -