Anti-PD-1 antibody enhances homeostatic proliferation-induced antitumor immunity during lymphopenia recovery

Zike Yang ^1* Ying Zhu ² Qian Wang ² Qing Lin ¹ Yahui Liu ²

• ¹ Zhongshan Hospital, Xiamen University, Xiamen, China
• ² Southern Medical University, Guangzhou, Guangdong, China

Lymphopenic condition after radiotherapy or chemotherapy could create an environment to induce an efficient antitumor immunity through the homeostatic proliferation of residual or adoptive lymphocytes. However, the antitumor immunity decreased rapidly with tumor growth, and the mechanism remained elusive. The aim of this study is to investigate the role of PD-1 signaling upon homeostatic proliferation-induced antitumor immunity in malignant melanoma. In this study, we found that although T cells proliferated continuously in lymphopenic mice, the number of IFN-γ-releasing CD8 + T cells rapidly decreased in course of homeostatic proliferation. The expression of PD-1 on T cells, increased gradually in course of homeostatic proliferation, were significantly negatively related to the cytotoxicity of effector T cells. Blocking of PD-1/PD-L1 axis by PD-1 antibody promoted homeostasis proliferating(HP) T cells to recognize tumor associated antigen (TAA) and resulted in the activation of DC cells. It can also enhanced the number of IFN-γ -releasing CD8 + T cells and the cytotoxicity of effector T cells and induced a portion of tumor-specific effector T cells convert to central memory T cells. These findings suggested that the PD-1/PD-L1 axis plays a crucial role in immune tolerance formation during homeostatic proliferation. Anti-PD-1 therapies might be used to enhance antitumor immunity during recovery from lymphopenia after chemotherapy or radiotherapy.