The introduction of immunotherapy revolutionized the treatment landscape in metastatic melanoma. Despite the impressive results associated with immune checkpoint inhibitors (ICIs), only a portion of patients obtain a response to this treatment. In this scenario, the research of predictive factors is fundamental to identify patients who may have a response and to exclude patients with a low possibility to respond. These factors can be host-associated, immune system activation-related, and tumor-related. Patient-related factors can vary from data obtained by medical history (performance status, age, sex, body mass index, concomitant medications, and comorbidities) to analysis of the gut microbiome from fecal samples. Tumor-related factors can reflect tumor burden (metastatic sites, lactate dehydrogenase, C-reactive protein, and circulating tumor DNA) or can derive from the analysis of tumor samples (driver mutations, tumor-infiltrating lymphocytes, and myeloid cells). Biomarkers evaluating the immune system activation, such as IFN-gamma gene expression profile and analysis of circulating immune cell subsets, have emerged in recent years as significantly correlated with response to ICIs. In this manuscript, we critically reviewed the most updated literature data on the landscape of predictive factors in metastatic melanoma treated with ICIs. We focus on the principal limits and potentiality of different methods, shedding light on the more promising biomarkers.
免疫疗法的引入彻底改变了转移性黑色素瘤的治疗格局。尽管免疫检查点抑制剂（ICIs）取得了令人瞩目的疗效，但仅有一部分患者能对此治疗产生应答。在此背景下，寻找预测性因素对于识别可能产生应答的患者以及排除应答可能性低的患者至关重要。这些因素可分为宿主相关因素、免疫系统激活相关因素以及肿瘤相关因素。患者相关因素涵盖从病史数据（体能状态、年龄、性别、体重指数、合并用药及并发症）到粪便样本中肠道微生物组分析等多个维度。肿瘤相关因素既可反映肿瘤负荷（转移部位、乳酸脱氢酶、C-反应蛋白及循环肿瘤DNA），也可源自肿瘤样本分析（驱动基因突变、肿瘤浸润淋巴细胞及髓系细胞）。评估免疫系统激活的生物标志物，如干扰素-γ基因表达谱和循环免疫细胞亚群分析，近年来已被证实与ICIs的应答显著相关。本文系统评述了关于ICIs治疗转移性黑色素瘤预测因素的最新文献数据，重点探讨不同方法的主要局限性与潜在价值，并对更具前景的生物标志物进行展望。
肿瘤(癌症)患者之家