Adiponectin‐expressing Treg‐containing T cell fraction inhibits tumor growth in orthotopically implanted triple‐negative breast cancer

Author:

Chikaishi Wakana1,Higashi Toshiya1,Hayashi Hirokatsu1,Hanamatsu Yuki2ORCID,Futamura Manabu3,Matsuhashi Nobuhisa1,Saigo Chiemi245ORCID,Takeuchi Tamotsu25ORCID

Affiliation:

1. Department of Gastroenterological Surgery and Pediatric Surgery Gifu University Graduate School of Medicine Gifu Japan

2. Department of Pathology and Translational Research Gifu University Graduate School of Medicine Gifu Japan

3. Department of Breast Surgery Gifu University Hospital Gifu Japan

4. The United Graduate School of Drug Discovery and Medical Information Sciences Gifu University Gifu Japan

5. Center for One Medicine Innovative Translational Research; COMIT Gifu University Gifu Japan

Abstract

AbstractBackgroundIn our previous study, we identified a population of adiponectin expressing regulatory T cells (Tregs) residing within thymic nurse cell complexes, which were capable of inhibiting the development of breast cancer in vitro. Triple‐negative breast cancer (TNBC) with no proper treatment at present is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor‐2. In this study, we aimed to investigate the potential of a cultured T cell fraction comprising adiponectin‐expressing Tregs, referred to as A‐TregTF (adiponectin‐expressing Treg‐containing T cell fraction), in inhibiting the progression of TNBC in vivo.MethodsThe efficacy of a spontaneously expanding T cell fraction comprising adiponectin‐expressing Treg in inhibiting tumor growth was analyzed in a murine orthotopic 4 T1‐Luc TNBC model.ResultsThe treatment with T cell fraction containing adiponectin‐expressing Tregs significantly inhibited the growth and metastasis of orthotopically transplanted 4 T1‐Luc tumor cells. Histopathological examination further revealed that the adiponectin‐expressing Tregs infiltrated the tumor tissue via a cell‐in‐cell mechanism and were found to be specifically localized around the necrotic areas.ConclusionsBased on our findings, the T cell fraction comprising adiponectin‐expressing Tregs, represents a potential candidate for adoptive cell therapy against TNBC.

Funder

Kaken

Publisher

Wiley

Subject

Pulmonary and Respiratory Medicine,Oncology,General Medicine

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