Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy.
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.
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Jae-Hyun
JH
Park
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Miran
M
Jang
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Yunus Emre
YE
Tarhan
Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
Toyomasa
T
Katagiri
Department of Surgery, Tokushima Breast Care Clinic, Tokushima 770-0052, Japan.
Mitsunori
M
Sasa
Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Yasuo
Y
Miyoshi
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Krishna R
KR
Kalari
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Vera J
VJ
Suman
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Richard
R
Weinshilboum
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Liewei
L
Wang
Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Judy C
JC
Boughey
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Matthew P
MP
Goetz
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Yusuke
Y
Nakamura
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000276:immunology
D011948:Receptors, Antigen, T-Cell