肿瘤细胞治疗研究
英文原题：Complete Remission of Hepatocellular Carcinoma With Atezolizumab and Bevacizumab Following Prior B-cell Depletion.
免疫检查点抑制剂（ICI）是不可切除肝细胞癌（HCC）的成熟疗法，其中 atezolizumab/bevacizumab 和 durvalumab/tremelimumab 已显示出临床疗效。
免疫检查点抑制剂（ICI）已成为不可切除肝细胞癌（HCC）的标准疗法，阿替利珠单抗联合贝伐珠单抗以及度伐利尤单抗联合曲美木单抗均显示出临床疗效。除激活CD8+ T细胞外，抗PD-(L)1疗法还可通过激活B细胞和形成三级淋巴结构来刺激体液免疫。然而，ICI也可能引发免疫相关不良事件（irAE），部分患者需接受抗CD20治疗，这引发了B细胞清除是否会影响后续ICI疗效的疑问。本文报告一例70多岁患者同时患有弥漫大B细胞淋巴瘤（DLBCL）和HCC，并先后接受R-CHOP及阿替利珠单抗联合贝伐珠单抗治疗后取得成功。患者接受6个周期R-CHOP治疗DLBCL后达到完全代谢缓解，但HCC复发。流式细胞术显示，R-CHOP治疗后患者出现B细胞清除和低丙种球蛋白血症。开始阿替利珠单抗联合贝伐珠单抗治疗后，甲胎蛋白（AFP）水平迅速下降，并证实肿瘤完全缓解。值得注意的是，ICI治疗后NK细胞比例升高，提示免疫活化增强。本病例显示，既往利妥昔单抗诱导的B细胞清除并未损害抗PD-L1疗法治疗HCC的疗效，并提示NK细胞可能在免疫治疗期间介导抗肿瘤免疫。
Immune checkpoint inhibitors (ICIs) are established therapies for unresectable hepatocellular carcinoma (HCC), with atezolizumab/bevacizumab and durvalumab/tremelimumab demonstrating clinical efficacy. Beyond activating CD8+ T cells, anti-PD(L)-1 therapies stimulate humoral immunity through B-cell activation and tertiary lymphoid structures. However, ICIs can also cause immune-related adverse events (irAEs), some managed with anti-CD20 therapy, raising concerns about whether B-cell depletion impacts subsequent ICI efficacy. This report presents a novel case of dual malignancies-diffuse large B-cell lymphoma (DLBCL) and HCC-in a patient in their 70s successfully treated with sequential R-CHOP and atezolizumab/bevacizumab. Following 6 cycles of R-CHOP for DLBCL, the patient achieved a complete metabolic response but developed recurrent HCC. Flow cytometry revealed B-cell depletion and hypogammaglobulinemia after R-CHOP. Upon initiation of atezolizumab/bevacizumab, AFP levels rapidly declined, and complete tumor remission was confirmed. Notably, NK cell percentages increased following ICI therapy, suggesting enhanced immune activation. This case demonstrates that prior rituximab-induced B-cell depletion does not impair the efficacy of anti-PD-L1 therapy in HCC and highlights the potential role of NK cells in mediating antitumor immunity during immunotherapy.
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