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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
  • View Affiliations / Copyright

    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
    Copyright: © Tamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3643-3649
    |
    Published online on: April 19, 2016
       https://doi.org/10.3892/ol.2016.4465
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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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1 

Zitvogel L, Kepp O and Kroemer G: Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol. 8:151–160. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Zitvogel L, Galluzzi L, Smyth MJ and Kroemer G: Mechanism of action of conventional and targeted anticancer therapies: Reinstating immunosurveillance. Immunity. 39:74–88. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, et al: Effector memory T cells, early metastasis and survival in colorectal cancer. N Engl J Med. 353:2654–2666. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Galon J, Costes A, Sanchez-Cabo F, et al: Type, density and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313:1960–1964. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Laghi L, Bianchi P, Miranda E, et al: CD3+ cells at the invasive margin of deeply invading (pT3-T4) colorectal cancer and risk of post-surgical metastasis: A longitudinal study. Lancet Oncol. 10:877–884. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Fridman WH, Pagès F, Sautes-Fridman C and Galon J: The immune contexture in human tumours: Impact on clinical outcome. Nat Rev Cancer. 12:298–306. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Yasuda K, Nirei T, Sunami E, Nagawa H and Kitayama J: Density of CD4(+) and CD8(+) T lymphocytes in biopsy samples can be a predictor of pathological response to chemoradiotherapy (CRT) for rectal cancer. Radiat Oncol. 6:492011. View Article : Google Scholar : PubMed/NCBI

8 

Rosenberg SA, Yang JC and Restifo NP: Cancer immunotherapy: Moving beyond current vaccines. Nat Med. 10:909–915. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Gajewski TF, Schreiber H and Fu YX: Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 14:1014–1022. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Poggi A, Musso A, Dapino I and Zocchi MR: Mechanisms of tumor escape from immune system: Role of mesenchymal stromal cells. Immunol Lett. 159:55–72. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Janeway CA Jr, Travers P, Walport M and Shlomchik MJ: Immunobiology: The Immune System in Health and Disease (5th). Garland Science. New York: 2001.

12 

Morris GP and Allen PM: How the TCR balances sensitivity and specificity for the recognition of self and pathogens. Nat Immunol. 13:121–128. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J and Kourilsky P: A direct estimate of the human alphabeta T cell receptor diversity. Science. 286:958–961. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J and Kourilsky P: Diversity of human alpha beta T cell receptors. Science. 288:11352000. View Article : Google Scholar : PubMed/NCBI

15 

Thor Straten P, Schrama D, Andersen MH and Becker JC: T-cell clonotypes in cancer. J Transl Med. 2:112004. View Article : Google Scholar : PubMed/NCBI

16 

Hazama S, Nakamura Y, Tanaka H, Hirakawa K, Tahara K, Shimizu R, Ozasa H, Etoh R, Sugiura F, Okuno K, et al: A phase II study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study). J Transl Med. 12:1082014. View Article : Google Scholar : PubMed/NCBI

17 

Fang H, Yamaguchi R, Liu X, Daigo Y, Yew PY, Tanikawa C, Matsuda K, Imoto S, Miyano S and Nakamura Y: Quantitative T cell repertoire analysis by deep cDNA sequencing of T cell receptor α and β chains using next-generation sequencing (NGS). Oncoimmunology. 3:e9684672015. View Article : Google Scholar : PubMed/NCBI

18 

Giudicelli V, Chaume D and Lefranc MP: IMGT/GENE-DB: A comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res. 33:D256–D261. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Langmead B and Salzberg SL: Fast gapped-read alignment with Bowtie 2. Nat Methods. 9:357–359. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Yousfi Monod M, Giudicelli V, Chaume D and Lefranc MP: IMGT/JunctionAnalysis: The first tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J JUNCTIONs. Bioinformatics. 20(Suppl 1): S379–S385. 2004. View Article : Google Scholar

21 

Venturi V, Kedzierska K, Turner SJ, Doherty PC and Davenport MP: Methods for comparing the diversity of samples of the T cell receptor repertoire. J Immunol Methods. 321:182–195. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Ochsenreither S, Fusi A, Wojtke S, Busse A, Nüssler NC, Thiel E, Keilholz U and Nagorsen D: Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients. J Transl Med. 8:352010. View Article : Google Scholar : PubMed/NCBI

23 

Sherwood AM, Emerson RO, Scherer D, Habermann N, Buck K, Staffa J, Desmarais C, Halama N, Jaeger D, Schirmacher P, et al: Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue. Cancer Immunol Immunother. 62:1453–1461. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Luo W, Liao WJ, Huang YT, Shi M, Zhang Y, Wen Q, Zhou MQ and Ma L: Normalization of T cell receptor repertoire diversity in patients with advanced colorectal cancer who responded to chemotherapy. Cancer Sci. 102:706–712. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Zhou J, Ma R, Luo R, Sun Y, He X, Sun W, Tang W and Yao X: Primary exploration of CDR3 spectratyping and molecular features of TCR β chain in the peripheral blood and tissue of patients with colorectal carcinoma. Cancer Epidemiol. 34:733–740. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pagès F and Galon J: Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 29:610–618. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Nagorsen D, Keilholz U, Rivoltini L, Schmittel A, Letsch A, Asemissen AM, Berger G, Buhr HJ, Thiel E and Scheibenbogen C: Natural T-cell response against MHC class I epitopes of epithelial cell adhesion molecule, her-2/neu and carcinoembryonic antigen in patients with colorectal cancer. Cancer Res. 60:4850–4854. 2000.PubMed/NCBI

28 

Czerkinsky C, Andersson G, Ekre HP, et al: Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods. 110:29–36. 1988. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tamura K, Hazama S, Yamaguchi R, Imoto S, Takenouchi H, Inoue Y, Kanekiyo S, Shindo Y, Miyano S, Nakamura Y, Nakamura Y, et al: Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer. Oncol Lett 11: 3643-3649, 2016.
APA
Tamura, K., Hazama, S., Yamaguchi, R., Imoto, S., Takenouchi, H., Inoue, Y. ... Kiyotani, K. (2016). Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer. Oncology Letters, 11, 3643-3649. https://doi.org/10.3892/ol.2016.4465
MLA
Tamura, K., Hazama, S., Yamaguchi, R., Imoto, S., Takenouchi, H., Inoue, Y., Kanekiyo, S., Shindo, Y., Miyano, S., Nakamura, Y., Kiyotani, K."Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer". Oncology Letters 11.6 (2016): 3643-3649.
Chicago
Tamura, K., Hazama, S., Yamaguchi, R., Imoto, S., Takenouchi, H., Inoue, Y., Kanekiyo, S., Shindo, Y., Miyano, S., Nakamura, Y., Kiyotani, K."Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer". Oncology Letters 11, no. 6 (2016): 3643-3649. https://doi.org/10.3892/ol.2016.4465
Copy and paste a formatted citation
x
Spandidos Publications style
Tamura K, Hazama S, Yamaguchi R, Imoto S, Takenouchi H, Inoue Y, Kanekiyo S, Shindo Y, Miyano S, Nakamura Y, Nakamura Y, et al: Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer. Oncol Lett 11: 3643-3649, 2016.
APA
Tamura, K., Hazama, S., Yamaguchi, R., Imoto, S., Takenouchi, H., Inoue, Y. ... Kiyotani, K. (2016). Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer. Oncology Letters, 11, 3643-3649. https://doi.org/10.3892/ol.2016.4465
MLA
Tamura, K., Hazama, S., Yamaguchi, R., Imoto, S., Takenouchi, H., Inoue, Y., Kanekiyo, S., Shindo, Y., Miyano, S., Nakamura, Y., Kiyotani, K."Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer". Oncology Letters 11.6 (2016): 3643-3649.
Chicago
Tamura, K., Hazama, S., Yamaguchi, R., Imoto, S., Takenouchi, H., Inoue, Y., Kanekiyo, S., Shindo, Y., Miyano, S., Nakamura, Y., Kiyotani, K."Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer". Oncology Letters 11, no. 6 (2016): 3643-3649. https://doi.org/10.3892/ol.2016.4465
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