Anti-PD1 therapy achieved better outcomes in non-liver cancer patients with HBV infection

Abstract Anti-PD1 therapy has shown promising outcomes in different types of cancer. It is valuable to analyze whether the efficacy of anti-PD1 therapy has been impacted in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer cannot be neglected. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD1 therapy on non-liver cancer patients infected with HBV. In addition, we performed single-cell RNA-seq (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients to compare the responses of HBV + ESCC patients and HBV- ESCC patients to anti-PD1 therapy. We found anti-PD1 therapy achieved better outcomes in HBV + non-liver cancer patients than their HBV- counterparts. Further analysis showed cytotoxicity of T cells and antigen presentation capacity of B cells significantly increased after anti-PD1 therapy in the 2 HBV + ESCC patients. We also identified CX3CR1high TEFF, a subset of CD8+ TEFF, associated with better clinical outcome of HBV + patients. Lastly, we found CD8+ TEFF from HBV + patients have higher fraction of Exhaustionhi T and lower cytotoxicity score than their HBV- counterpart. In summary, Anti-PD1 therapy on HBV + non-liver patients is safe and achieves better outcomes than that on HBV- non-liver patients, potentially because HBV + patients had stronger immunosuppression which made them more efficiently respond to anti-PD1 therapy.