Strobel Sophia B, Machiraju Devayani, Wiecken Melanie, Richter Jasmin, Klein Julian A F, Berger Annemarie, Hassel Jessica C
Department of Dermatology and National Center for Tumor Diseases (NCT), Medical Faculty Heidelberg, NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Cancer Immunol Immunother. 2025 Jan 3;74(2):59. doi: 10.1007/s00262-024-03859-3.
Cytomegalovirus (CMV) infection or reactivation in immune-compromised individuals can lead to a wide range of severe complications including hepatitis. However, its relation with immune checkpoint inhibitors (ICIs) induced hepatitis (ICI-hepatitis) and tumor responses in advanced melanoma patients remains unclear. Hundred and ninety metastatic cutaneous melanoma patients (mCM) who received ICI treatment, with CMV IgG or IgM information available at baseline, were included in the study (Cohort 1). Clinical characteristics and immune cell count in the blood were retrieved from medical records. In addition, anti-CMV IgG and IgM were measured in pre and on-treatment serum samples from 49 advanced skin cancer patients using ELISA (Cohort 2). In the event of a positive anti-CMV IgM, further analysis with PCR was performed. Univariate and multivariate analysis was used to assess the relationship between CMV IgG or IgM and ICI-hepatitis tumor outcomes. Twenty-one patients (11%) developed hepatitis during ICI treatment (Cohort 1). ICI-hepatitis was significantly associated with disease control rate (DCR; p = 0.017) and longer progression-free survival (PFS; p = 0.008) in mCM patients. Detection of CMV IgG or IgM antibodies were not associated with ICI-hepatitis (p > 0.05). However, increased CMV IgG values at baseline correlated with disease progression (p = 0.047) and shorter PFS (p = 0.081). In addition, increased CMV IgG values were associated with reduced levels of monocytes (p = 0.005), eosinophils (p = 0.062), and neutrophils (p = 0.065) in the blood. In summary, anti-CMV IgG or IgM in the blood may not be associated with ICI-hepatitis, but high anti-CMV IgG at baseline indicates poor outcomes in ICI-treated mCM patients.
巨细胞病毒（CMV）感染或在免疫功能低下个体中的再激活可导致包括肝炎在内的多种严重并发症。然而，其与免疫检查点抑制剂（ICI）诱导的肝炎（ICI-肝炎）以及晚期黑色素瘤患者肿瘤反应之间的关系仍不明确。本研究纳入了190例接受ICI治疗且基线时可获得CMV IgG或IgM信息的转移性皮肤黑色素瘤患者（mCM）（队列1）。从病历中获取临床特征和血液中的免疫细胞计数。此外，使用酶联免疫吸附测定（ELISA）检测了49例晚期皮肤癌患者治疗前和治疗期间血清样本中的抗CMV IgG和IgM（队列2）。若抗CMV IgM呈阳性，则进一步进行聚合酶链反应（PCR）分析。采用单因素和多因素分析评估CMV IgG或IgM与ICI-肝炎肿瘤结局之间的关系。21例患者（11%）在ICI治疗期间发生肝炎（队列1）。在mCM患者中，ICI-肝炎与疾病控制率（DCR；p = 0.017）和更长的无进展生存期（PFS；p = 0.008）显著相关。CMV IgG或IgM抗体的检测与ICI-肝炎无关（p > 0.05）。然而，基线时CMV IgG值升高与疾病进展（p = 0.047）和较短的PFS（p = 0.081）相关。此外，CMV IgG值升高与血液中单核细胞（p = 0.005）、嗜酸性粒细胞（p = 0.062）和中性粒细胞（p = 0.065）水平降低相关。总之，血液中的抗CMV IgG或IgM可能与ICI-肝炎无关，但基线时高抗CMV IgG表明接受ICI治疗的mCM患者预后不良。
