期刊
CANCER IMMUNOLOGY RESEARCH
卷 6, 期 2, 页码 151-162出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-17-0114
关键词
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资金
- NIH [R01-AI44129, CA108835, U01 AI113315]
- Bristol Myers-Squibb
- Pershing Square Sohn Cancer Research Foundation
- PaineWebber Chair
- Stand Up To Cancer
- STARR Cancer Consortium
- MSK Core Grant [P30 CA008748]
- Stand Up To Cancer - American Cancer Society Lung Cancer Dream Team Translational Research Grant [SU2C-AACR-DT17-15]
- American Association for Cancer Research, the scientific partner of SU2C
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.
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