Takada Hitomi, Osawa Leona, Komiyama Yasuyuki, Muraoka Masaru, Suzuki Yuichiro, Sato Mitsuaki, Kobayashi Shoji, Yoshida Takashi, Takano Shinichi, Maekawa Shinya, Enomoto Nobuyuki
Gastroenterology and Hepatology Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Oncology. 2025;103(1):37-47. doi: 10.1159/000540648. Epub 2024 Jul 30.
Atezolizumab plus bevacizumab (AB) therapy was the effective immune checkpoint inhibitor (ICI) for unresectable hepatocellular carcinoma (u-HCC). However, immune-related adverse events (irAEs) are common in patients receiving ICI therapies. Our research aimed to explore the risk factors for irAE development, with attention to interleukin-7 (IL-7) risk alleles, lymphocyte counts, and autoantibodies.
Seventy-six patients receiving AB therapy for u-HCC were recruited. Single nucleotide polymorphism genotyping was done for the analysis of rs16906115 polymorphism near IL-7-expressing genes using 20 μL of stored buffy coat at baseline. The association between IL-7 risk alleles, lymphocyte counts, autoantibodies, and irAE development was investigated.
irAEs were found in 14 (18%) patients. The incidence of irAEs did not differ significantly between the groups showing IL-7 AG/AA and the GG group (p = 0.72). The incidence in the group with a lymphocyte count of 1,130/µL or more at baseline was higher than in that with a value below 1,130/µL (p = 0.0093). The group showing IL-7 AG/AA or lymphocyte count >1,130/μL had a higher irAE prevalence rate than the others (p = 0.019). IL-7 AG/AA or lymphocyte count >1,130/μL and positivity for autoantibodies at baseline were the prognostic factors for irAE development. irAE incidence could be stratified using a combination of IL-7 AG/AA or lymphocyte counts ≥1,130/µL and positive autoantibodies (p = 0.016).
Patients with IL-7 risk alleles, high lymphocyte counts, and autoantibodies at baseline may require careful monitoring for irAE development.
阿替利珠单抗联合贝伐单抗（AB）疗法是治疗不可切除肝细胞癌（u-HCC）的有效免疫检查点抑制剂（ICI）。然而，免疫相关不良事件（irAE）在接受ICI治疗的患者中很常见。我们的研究旨在探讨irAE发生的危险因素，重点关注白细胞介素-7（IL-7）风险等位基因、淋巴细胞计数和自身抗体。
招募了76例接受AB疗法治疗u-HCC的患者。使用基线时储存的20μL血沉棕黄层进行单核苷酸多态性基因分型，以分析IL-7表达基因附近的rs16906115多态性。研究了IL-7风险等位基因、淋巴细胞计数、自身抗体与irAE发生之间的关联。
14例（18%）患者出现irAE。显示IL-7 AG/AA的组与GG组之间irAE的发生率无显著差异（p = 0.72）。基线时淋巴细胞计数为1130/µL或更高的组的发生率高于低于1130/µL的组（p = 0.0093）。显示IL-7 AG/AA或淋巴细胞计数>1130/μL的组的irAE患病率高于其他组（p = 0.019）。IL-7 AG/AA或淋巴细胞计数>1130/μL以及基线时自身抗体呈阳性是irAE发生的预后因素。可使用IL-7 AG/AA或淋巴细胞计数≥1130/µL与自身抗体阳性的组合对irAE发生率进行分层（p = 0.016）。
基线时具有IL-7风险等位基因、高淋巴细胞计数和自身抗体的患者可能需要密切监测irAE的发生。
