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

Jae Hyun Park, Miran Jang, Yunus Emre Tarhan, Toyomasa Katagiri, Mitsunori Sasa, Yasuo Miyoshi, Krishna R Kalari, Vera Jean Suman, Richard M Weinshilboum, Liewei M Wang, Judy C Boughey, Matthew Philip Goetz, Yusuke Nakamura

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 TCR 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.

Original languageEnglish (US)
Pages (from-to)471-478
Number of pages8
JournalInternational Journal of Oncology
Volume49
Issue number2
DOIs
StatePublished - Aug 1 2016

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Breast Neoplasms
T-Lymphocytes
Drug Therapy
T-Cell Antigen Receptor
Neoplasms
Tumor Microenvironment
Therapeutics
Recurrence
Polymerase Chain Reaction

Keywords

  • Biomarker
  • Breast cancer
  • T cell receptor
  • Tumor immunity
  • Tumor-infiltrating T cell

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Park, J. H., Jang, M., Tarhan, Y. E., Katagiri, T., Sasa, M., Miyoshi, Y., ... Nakamura, Y. (2016). Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy. International Journal of Oncology, 49(2), 471-478. https://doi.org/10.3892/ijo.2016.3540

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 Jean; Weinshilboum, Richard M; Wang, Liewei M; Boughey, Judy C; Goetz, Matthew Philip; Nakamura, Yusuke.

In: International Journal of Oncology, Vol. 49, No. 2, 01.08.2016, p. 471-478.

Research output: Contribution to journalArticle

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