Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Int J Mol Sci. 2024 Oct 11;25(20):10958. doi: 10.3390/ijms252010958.
Atezolizumab and bevacizumab show promise for treating hepatocellular carcinoma (HCC), but identifying responsive patients remains challenging, due to tumor heterogeneity. This study explores immune dynamics following this combination therapy. Between 2020 and 2023, 29 patients with advanced HCC who received atezolizumab plus bevacizumab at Severance Hospital, Seoul, were enrolled in this study. Peripheral blood mononuclear cells were analyzed using flow cytometry and statistical methods to assess immune alterations and identify biomarkers. Baseline characteristics showed a diverse HCC cohort with a mean age of 64 years and 82.8% male predominance. Absence of extrahepatic metastasis was associated with better overall survival. Immune responses revealed distinct CD4 T-cell phenotypes between the 'partial response (PR) + stable disease (SD)' and 'progressive disease (PD)' groups, with an overall increase in CD8 T-cell phenotypes. Patients with higher frequencies of CD8PD-1Ki-67 T cells experienced significantly improved overall survival, while those with lower frequencies of CD4Foxp3PD-1LAG3 T cells also had notable survival benefits. These findings enhance the overall understanding of immune responses to this combination therapy, facilitating improved patient stratification and personalized therapeutic approaches for HCC.
阿替利珠单抗联合贝伐珠单抗有望治疗肝细胞癌(HCC),但由于肿瘤异质性,确定有反应的患者仍然具有挑战性。本研究探讨了联合治疗后的免疫动力学。2020 年至 2023 年期间,在首尔 Severance 医院接受阿替利珠单抗联合贝伐珠单抗治疗的 29 名晚期 HCC 患者被纳入本研究。采用流式细胞术和统计方法分析外周血单核细胞,以评估免疫改变并确定生物标志物。基线特征显示 HCC 队列具有异质性,平均年龄为 64 岁,男性占 82.8%。无肝外转移与总生存期更好相关。免疫反应显示“部分缓解(PR)+稳定疾病(SD)”和“进展性疾病(PD)”两组之间存在不同的 CD4 T 细胞表型,CD8 T 细胞表型总体增加。CD8PD-1Ki-67 T 细胞频率较高的患者总生存期显著改善,而 CD4Foxp3PD-1LAG3 T 细胞频率较低的患者也有显著的生存获益。这些发现增强了对这种联合治疗免疫反应的整体理解,有助于改善 HCC 患者的分层和个性化治疗方法。