Merkel cell carcinoma (MCC) is primarily a disease of the elderly Caucasian, with most cases occurring in individuals over 50. Immune checkpoint inhibitors (ICI) treatment has shown promising results in MCC patients. Although ~34% of MCC patients are expected to exhibit at least one of the predictive biomarkers (PD-L1, high tumor mutational burden/TMB-H/, and microsatellite instability), their clinical significance in MCC is not fully understood. PD-L1 expression has been variably described in MCC, but its predictive value has not been established yet. Our literature survey indicates conflicting results regarding the predictive value of TMB in ICI therapy for MCC. Avelumab therapy has shown promising results in Merkel cell polyomavirus (MCPyV)-negative MCC patients with TMB-H, while pembrolizumab therapy has shown better response in patients with low TMB. A study evaluating neoadjuvant nivolumab therapy found no significant difference in treatment response between the tumor etiologies and TMB levels. In addition to ICI therapy, other treatments that induce apoptosis, such as milademetan, have demonstrated positive responses in MCPyV-positive MCC, with few somatic mutations and wild-typeTP53. This review summarizes current knowledge and discusses emerging and potentially predictive biomarkers for MCC therapy with ICI.
默克尔细胞癌（MCC）主要见于老年白种人，多数病例发生于50岁以上人群。免疫检查点抑制剂（ICI）治疗在MCC患者中显示出良好疗效。尽管约34%的MCC患者预计会呈现至少一种预测性生物标志物（PD-L1、高肿瘤突变负荷/TMB-H/和微卫星不稳定性），但这些标志物在MCC中的临床意义尚未完全明确。PD-L1在MCC中的表达情况存在不同报道，但其预测价值尚未确立。文献调研显示，TMB在MCC的ICI治疗中的预测价值存在矛盾结果：Avelumab治疗在TMB-H且默克尔细胞多瘤病毒（MCPyV）阴性的MCC患者中疗效显著，而Pembrolizumab治疗在低TMB患者中反应更佳。一项评估新辅助Nivolumab治疗的研究发现，不同肿瘤病因和TMB水平患者的治疗反应无显著差异。除ICI治疗外，其他诱导细胞凋亡的治疗方法（如Milademetan）在MCPyV阳性、体细胞突变较少且TP53野生型的MCC中也显示出积极反应。本综述总结了现有认知，并探讨了MCC的ICI治疗中新兴且具有潜在预测价值的生物标志物。
肿瘤(癌症)患者之家