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.

抗 PD-1 疗法在治疗不同类型的癌症方面显示出可喜的成果。由于 HBV 和癌症的合并症已被广泛记录，因此分析抗 PD-1 疗法对感染乙型肝炎病毒 (HBV) 的癌症患者的疗效具有根本意义。我们设计了一项多中心回顾性研究，以评估抗 PD-1 疗法对感染 HBV 的非肝癌患者的疗效。我们发现抗 PD-1 疗法在 HBV+ 非肝癌患者中取得的结果比他们的 HBV- 对应物好得多。我们对来自食管鳞状细胞癌 (ESCC) 患者的外周血单核细胞 (PBMC) 进行了单细胞 RNA 测序 (scRNA-seq)。我们发现在 HBV + ESCC 患者中进行抗 PD-1 治疗后，T 细胞的细胞毒性评分和 B 细胞的 MHC 评分均显着增加。^高T _EFF是 CD8 ⁺ T _EFF的一个子集，与 HBV + ESCC 患者更好的临床结果相关。最后，我们发现来自 HBV+ ESCC 患者的 CD8 ⁺ T _EFF显示出比 HBV- 患者更高的 Exhaustion ^{hi T 分数。}总之，与 HBV- 非肝癌患者相比，HBV+ 非肝癌患者的抗 PD-1 治疗是安全的并且取得了更好的结果，这可能是因为 HBV+ 患者具有更高的 Exhaustion hi T 分数，这使得他们^更有效对抗 PD-1 疗法有反应。