1. Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy
- Author
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Toyomasa Katagiri, Richard M. Weinshilboum, Yunus Emre Tarhan, Vera J. Suman, Mitsunori Sasa, Krishna R. Kalari, Judy C. Boughey, Yasuo Miyoshi, Miran Jang, Matthew P. Goetz, Yusuke Nakamura, Liewei Wang, and Jae-Hyun Park
- Subjects
Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,T-Lymphocytes ,Receptors, Antigen, T-Cell ,Breast Neoplasms ,chemical and pharmacologic phenomena ,Biology ,03 medical and health sciences ,breast cancer ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Breast cancer ,Antigen ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Microenvironment ,medicine ,Humans ,Aged ,Tumor microenvironment ,T-cell receptor ,Cancer ,FOXP3 ,Articles ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,tumor immunity ,3. Good health ,Treatment Outcome ,030104 developmental biology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Disease Progression ,biomarker ,tumor-infiltrating T cell ,Female ,T cell receptor ,CD8 - Abstract
The immune microenvironment of tumor plays a critical role in therapeutic responses to chemotherapy. Cancer tissues are composed of a complex network between anti-tumor 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.
- Published
- 2016