Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy

Park,Jae-Hyun; Jang,Miran; Tarhan,Yunus  Emre; Katagiri,Toyomasa; Sasa,Mitsunori; Miyoshi,Yasuo; Kalari,Krishna  R.; Suman,Vera  J.; Weinshilboum,Richard; Wang,Liewei; Boughey,Judy  C.; Goetz,Matthew  P.; Nakamura,Yusuke

doi:10.3892/ijo.2016.3540

Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy

Authors:
- Jae-Hyun Park
- Miran Jang
- Yunus Emre Tarhan
- Toyomasa Katagiri
- Mitsunori Sasa
- Yasuo Miyoshi
- Krishna R. Kalari
- Vera J. Suman
- Richard Weinshilboum
- Liewei Wang
- Judy C. Boughey
- Matthew P. Goetz
- Yusuke Nakamura
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Affiliations: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA, Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan, Department of Surgery, Tokushima Breast Care Clinic, Tokushima 770-0052, Japan, Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA, Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
Published online on: May 27, 2016 https://doi.org/10.3892/ijo.2016.3540
Pages: 471-478
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The immune microenvironment of tumor plays a critical role in therapeutic responses to chemotherapy. Cancer tissues are composed of a complex network between antitumor and pro-tumor immune cells and molecules; therefore a comprehensive analysis of the tumor immune condition is imperative for better understanding of the roles of the immune microenvironment in anticancer treatment response. In this study, we performed T cell receptor (TCR) repertoire analysis of tumor infiltrating T cells (TILs) in cancer tissues of pre- and post-neoadjuvant chemotherapy (NAC) from 19 breast cancer patients; five cases showed CR (complete response), ten showed PR (partial response), and four showed SD/PD (stable disease/progressive disease) to the treatment. From the TCR sequencing results, we calculated the diversity index of the TCRβ chain and found that clonal expansion of TILs could be detected in patients who showed CR or PR to NAC. Noteworthy, the diversity of TCR was further reduced in the post-NAC tumors of CR patients. Our quantitative RT-PCR also showed that expression ratio of CD8/Foxp3 was significantly elevated in the post-NAC tumors of CR cases (p=0.0032), indicating that antitumor T cells were activated and enriched in these tumors. Collectively, our findings suggest that the clonal expansion of antitumor T cells may be a critical factor associated with response to chemotherapy and that their TCR sequences might be applicable for the development of TCR-engineered T cells treatment for individual breast cancer patients when their tumors relapse.

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