Physical activity improves outcomes of combined lenvatinib plus anti-PD-1 therapy in unresectable hepatocellular carcinoma: a retrospective study and mouse model

作者：Xuefeng Liu, Xiao‐Dong Zhu, Long-Hai Feng, Xiaolong Li, Bin Xu, Kangshuai Li, Nan Xiao, Ming Lei, Hui‐Chuan Sun, Zhao–You Tang · 发表于：Experimental Hematology and Oncology · 年份：2022 · DOI：10.1186/s40164-022-00275-0 · 被引用次数：24 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer survivorship and care、Immune cells in cancer

BACKGROUND: Physical activity is known to have anti-cancer effects, including immunomodulatory actions. This study investigated the hypothesis that physical activity synergizes with combined lenvatinib plus anti-PD-1 therapy to enhance efficacy in patients with unresectable HCC. METHODS: The physical activity levels of patients with unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy were recorded by questionnaire. Patients were categorized according to physical activity levels (active vs. sedentary). The primary outcome was overall survival (OS). Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). A subcutaneous syngeneic HCC model was generated in C57BL/6 mice. Mice were randomized to receive placebo, combined lenvatinib plus anti-PD-1 antibodies or combination therapy plus physical activity. Tumors were measured every 3 days and harvested for immunohistochemistry analysis at 20 mm maximum diameter. RESULTS: Fifty-nine patients with unresectable HCC were categorized to active (n = 28) or sedentary (n = 31) groups. The active group had higher albumin and des-γ-carboxy prothrombin levels and lower hepatitis B virus load at baseline; other clinical and oncologic characteristics were comparable between the two groups. Patients in the active group had significantly longer OS (HR = 0.220, 95% CI 0.060-0.799) and PFS (HR = 0.158, 95% CI 0.044-0.562) and higher ORR (OR = 4.571, 95% CI 1.482-14.102) than patients in the se...