Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer

Tamura,Kenji; Hazama,Shoichi; Yamaguchi,Rui; Imoto,Seiya; Takenouchi,Hiroko; Inoue,Yuka; Kanekiyo,Shinsuke; Shindo,Yoshitaro; Miyano,Satoru; Nakamura,Yusuke; Kiyotani,Kazuma

doi:10.3892/ol.2016.4465

Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer

Authors:
- Kenji Tamura
- Shoichi Hazama
- Rui Yamaguchi
- Seiya Imoto
- Hiroko Takenouchi
- Yuka Inoue
- Shinsuke Kanekiyo
- Yoshitaro Shindo
- Satoru Miyano
- Yusuke Nakamura
- Kazuma Kiyotani
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Affiliations: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA, Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan
Published online on: April 19, 2016 https://doi.org/10.3892/ol.2016.4465
Pages: 3643-3649
Copyright: © Tamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to characterize infiltrated T cell clones that define the tumor immune environment and are important in the response to treatment in patients with advanced colorectal cancer (CRC). In order to explore predictive biomarkers for the efficacy of immunochemotherapies, T cell receptor (TCR) repertoire analysis was performed using blood samples and tumor tissues obtained from patients with advanced CRC that had been treated with a combination of five‑cancer peptide vaccines and oxaliplatin‑based chemotherapy. The TCR‑α/β complementary DNAs (cDNAs), prepared from the messenger RNAs (mRNAs) obtained from 17 tumor tissues and 39 peripheral blood mononuclear cells of 9 CRC patients at various time points, were sequenced. The oligoclonal enrichment of certain TCR sequences was identified in tumor tissues and blood samples; however, only a few TCR sequences with a frequency of >0.1% were commonly detected in pre‑ and post‑treatment tumor tissues, or in post‑treatment blood and tissue samples. The average correlation coefficients of the TCR‑α and TCR‑β clonotype frequencies between the post‑treatment tumor tissues and blood samples were 0.023 and 0.035, respectively, and were much lower compared with the correlation coefficients of the TCR‑α and TCR‑β clonotype frequencies between pre‑ and post‑treatment blood samples (0.430 and 0.370, respectively), suggesting that T cell populations in tumor tissues vary from those in blood. Although the sample size was small, a tendency for the TCR diversity in tumor tissues to drastically decrease during the treatment was indicated in two patients, who exhibited a longer progression‑free survival time. The results of the present study suggest that TCR diversity scores in tissues may be a useful predictive biomarker for the therapeutic effect of immunochemotherapy for patients with advanced CRC.

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