Potential activity of adiponectin‐expressing regulatory T cells against triple‐negative breast cancer cells through the cell‐in‐cell phenomenon

• Published in: Thoracic cancer 2023-07, Vol.14 (20), p.1941-1945
• Main Authors: Chikaishi, Wakana, Higashi, Toshiya, Hayashi, Hirokatsu, Hanamatsu, Yuki, Kito, Yusuke, Futamura, Manabu, Matsuhashi, Nobuhisa, Saigo, Chiemi, Takeuchi, Tamotsu
• Format: Article
• Language: English
• Subjects: adiponectin; Adiponectin - metabolism; adoptive cell therapy; Animals; Antibodies; Apoptosis; Breast cancer; Cells; cell‐in‐cell; Cloning; Dehydrogenases; Humans; Lasers; Lymphocytes; Membranes; Mice; Molecular weight; Obesity; Original; T-Lymphocytes, Regulatory; Treg; Triple Negative Breast Neoplasms; triple‐negative breast cancer; Tumors
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.14940

Background A population of regulatory T cells (Treg), which reside within thymic nurse cell complexes, express adiponectin and abrogate breast cancer development in transgenic mice. In this study, we examined whether adiponectin‐expressing Treg could impair triple‐negative breast cancer, which is defined by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor‐2. Methods CD4‐ and CD25‐positive cells were sorted from cultured T lymphocytes of a previously characterized experimental thymic tumor model composed of thymic nurse cells and abundant lymphoid stroma. These sorted cells were examined for FOXP3 and adiponectin immunoreactivity and subsequently exposed to triple‐negative breast cancer MDA‐MB‐157 and ‐231 cells. Results Adiponectin‐expressing Treg were obtained by CD4‐ and CD25‐positive sorting and cell death was induced in triple‐negative breast cancer cells through the cell‐in‐cell phenomenon. Conclusions Adiponectin‐expressing Treg may be candidates for adoptive cell therapy against triple‐negative breast cancer. Adiponectin‐expressing Treg induced cell death of triple‐negative breast cancer cells through the cell‐in‐cell phenomenon. Triple‐negative breast cancer cells were occulted with adiponectin‐expressing Treg. The cytoplasm of cancer cells was stained red, engulfed adiponectin‐expressing Treg stained green. Horizontal and vertical cell‐in‐cell images are shown in the upper left and lower left, respectively. Numerous adiponectin‐expressing Treg attached and integrated into cancer cells (upper right) subsequently destroyed cancer cells (lower right).