Cemiplimab 已在皮肤鳞状细胞癌 (cSCC) 中表现出相关的临床活性，但对免疫治疗的原发性和获得性耐药机制仍不清楚。我们收集了在两个意大利大学中心接受 cemiplimab 治疗的局部晚期和/或转移性 cSSC 患者的临床数据。此外，使用 Nanostring Technologies 平台进行基因表达分析，评估 20 个肿瘤组织样本（9 个对 cemiplimab 有反应者和 11 个无反应者）的 770 个癌症和免疫相关基因。我们招募了 81 名患者，中位年龄为 82 岁。中位随访 16.4 个月后，12 个月和 24 个月的 PFS 分别为 53% 和 42%； 12 个月和 24 个月的 OS 分别为 71% 和 61%。治疗耐受性良好。总缓解率 (ORR) 为 58%，疾病控制率 (DCR) 为 77.8%。有反应者与无反应者患者样本中表达的基因之间存在很大差异，特别是涉及免疫系统调节的基因。 Cemiplimab 耐药肿瘤与 CCL-20 和 CXCL-8 的过度表达相关。 Cemiplimab 证实了现实生活中 cSCC 患者的疗效和安全性数据。 CCL-20 和 CXCL-8 的过度表达可能代表对免疫疗法缺乏反应的生物标志物。© 2024 作者。经泰勒许可出版

Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.