Anti-PD-1 therapy achieves favorable outcomes in HBV-positive non-liver cancer

• Published in: Oncogenesis (New York, NY) Vol. 12; no. 1; p. 22
• Main Authors: Zhou, Jie, Chen, Guanming, Wang, Jiuling, Zhou, Bo, Sun, Xuemin, Wang, Jinsong, Tang, Shu, Xing, Xiangju, Hu, Xiaofei, Zhao, Yang, Peng, Yu, Shi, Wenjiong, Zhao, Tingting, Wu, Yuzhang, Zhong, Hanbing, Hong, Ni, Ruan, Zhihua, Zhang, Yi, Jin, Wenfei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2023; Nature Publishing Group
• Subjects: 38/91; 631/250/251; 631/67/580; Apoptosis; CD8 antigen; Cell Biology; Comorbidity; Cytotoxicity; Esophageal cancer; Hepatitis B; Human Genetics; Immunotherapy; Internal Medicine; Leukocytes (mononuclear); Liver cancer; Lymphocytes B; Lymphocytes T; Major histocompatibility complex; Medicine; Medicine & Public Health; Oncology; Patients; PD-1 protein; Peripheral blood mononuclear cells; Squamous cell carcinoma
• ISSN: 2157-9024; 2157-9024
• DOI: 10.1038/s41389-023-00468-0

Anti-PD-1 therapy has shown promising outcomes in the treatment of different types of cancer. It is of fundamental interest to analyze the efficacy of anti-PD-1 therapy in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer is widely documented. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD-1 therapy on non-liver cancer patients infected with HBV. We found anti-PD-1 therapy achieved much better outcomes in HBV+ non-liver cancer patients than their HBV– counterparts. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients. We found both cytotoxicity score of T cells and MHC score of B cells significantly increased after anti-PD-1 therapy in HBV+ ESCC patients. We also identified CX3CR1 high T EFF , a subset of CD8 + T EFF , associated with better clinical outcome in HBV+ ESCC patients. Lastly, we found CD8 + T EFF from HBV+ ESCC patients showing higher fraction of Exhaustion hi T than their HBV– counterpart. In summary, anti-PD-1 therapy on HBV+ non-liver cancer patients is safe and achieves better outcomes than that on HBV– non-liver cancer patients, potentially because HBV+ patients had higher fraction of Exhaustion hi T, which made them more efficiently respond to anti-PD-1 therapy.