Quantitative analysis and clonal characterization of T-cell receptor β repertoires in patients with advanced non-small cell lung cancer treated with cancer vaccine

Mai,Tu; Takano,Atsushi; Suzuki,Hiroyuki; Hirose,Takashi; Mori,Takahiro; Teramoto,Koji; Kiyotani,Kazuma; Nakamura,Yusuke; Daigo,Yataro

doi:10.3892/ol.2017.6125

Quantitative analysis and clonal characterization of T-cell receptor β repertoires in patients with advanced non-small cell lung cancer treated with cancer vaccine

Authors:
- Tu Mai
- Atsushi Takano
- Hiroyuki Suzuki
- Takashi Hirose
- Takahiro Mori
- Koji Teramoto
- Kazuma Kiyotani
- Yusuke Nakamura
- Yataro Daigo
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Affiliations: Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL 60637, USA, Department of Medical Oncology, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan, Department of Regenerative Surgery, Fukushima Medical University, School of Medicine, Fukushima 960‑1295, Japan, Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa‑ku, Tokyo 142‑8555, Japan, Tohoku Community Cancer Services Program, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8574, Japan, Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
Published online on: May 5, 2017 https://doi.org/10.3892/ol.2017.6125
Pages: 283-292

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Abstract

With the development of cancer immunotherapy that may activate T cells, a practical and quantitative method to improve monitoring and/or prediction of immunological response of patients as a predictive biomarker is of importance. To examine possible biomarkers for a therapeutic cancer vaccine containing a mixture of three epitope peptides derived from cell division‑associated 1, lymphocyte antigen 6 complex locus K and insulin‑like growth factor‑II mRNA‑binding protein 3, T‑cell receptor β (TCRβ) repertoires of blood samples from 24 patients with human leukocyte antigen‑A*2402‑positive non‑small cell lung cancer were characterized prior to and following 8 weeks of the cancer vaccine treatment, by applying a next‑generation sequencing method. It was identified that 14 patients with overall survival (OS) times of ≥12 months had significantly lower TCRβ diversity indexes in samples prior to treatment, compared with 10 patients who succumbed within 1 year (P=0.03). In addition, patients with a high level of activated CD8+ T cells that are defined by a high granzyme A/CD8 ratio had favorable OS rates (log‑rank test, P=0.04). The TCRβ diversity index and immunogenic gene markers following vaccine administration may serve as predictive or monitoring biomarkers for cancer vaccine treatment.

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