How to detour Treg cells in T cell-based antitumor immune therapy

Shu Zheng,¹ Yanwei Shen,^1,2 Yongmao Song,^1,3 Ying Yuan<sup>1,2

1</sup>The Cancer Institute, Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, ²Department of Medical Oncology, ³Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China

Abstract: T cell-based antitumor immune therapy which occupies the boosting area of translational medicine research is capable of eradicating some kinds of tumors that are in late stages. However, the effectiveness of adoptive cell transfer treatment varies among the different clinical trials, while the safety of cells is still uncertain for some patients. All these phenomena provoke us to ask whether the instability of T cell-based antitumor immune therapy is due to immune modulation function of Treg cells in the tumor microenvironment and the peripheral circulation. Some successful Treg-targeting treatments in clinical trials provide the inspiration for subtle modulation of Treg cells in future cancer immunotherapies. We hypothesized that Treg cells may somehow sense the abundance of peripheral immune effector cells, and maintain the shifted tumor-bearing homeostasis of the immune system. Killer cells infused in adoptive cell transfer therapy may be monitored and spontaneously downregulated by Treg cells. Further studies are required to develop more effective combinations of immunotherapy with conventional chemo/radiotherapy in the modulation of immune-suppressive cells.

Keywords: regulatory T lymphocytes, Treg cells, adoptive cell transfer, tumor immune tolerance, immune modulation, cytokine induction