CCL-20和CXCL-8基因的过表达增强了局部晚期和转移性皮肤细胞癌的患者，增强了对程序性细胞死亡蛋白-1（PD-1）抑制剂Cemiplimab的抗肿瘤逃生和抗性。
Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma
影响因子:6.30000
分区:医学2区 / 免疫学2区 肿瘤学2区
发表日期:2024
作者:
Vincenzo De Falco, Stefania Napolitano, Renato Franco, Federica Zito Marino, Luigi Formisano, Daniela Esposito, Gabriella Suarato, Rossella Napolitano, Alfonso Esposito, Francesco Caraglia, Maria Cristina Giugliano, Eleonora Cioli, Vincenzo Famiglietti, Roberto Bianco, Giuseppe Argenziano, Andrea Ronchi, Davide Ciardiello, Valerio Nardone, Emma D'Ippolito, Sara Del Tufo, Fortunato Ciardiello, Teresa Troiani
摘要
Cemiplimab在皮肤鳞状细胞癌（CSCC）中表现出相关的临床活性，但原发性和获得性免疫疗法的抗性机制仍然未知。我们从两个意大利大学中心接受Cemiplimab治疗的本地高级和/或转移性CSSC患者收集了临床数据。此外，对20个肿瘤组织样品（9个反应者和11个对Cemiplimab的无反应者）评估770个癌症和免疫相关基因的基因表达分析进行了评估。我们招募了81例中位年龄为82岁的患者。经过16.4个月的中位随访后，12个月和24个月的PFS分别为53％和42％。而12个月和24个月的OS分别为71％和61％。治疗的耐受性良好。总体反应率（ORR）为58％，疾病控制率（DCR）为77.8％。在响应者与非反应患者样本中表达的基因之间的差异是很大的，特别是对于参与免疫系统调节的基因。抗Cmiplimab的肿瘤与CCL-20和CXCL-8的过表达有关。 Cemiplimab证实了现实生活中CSCC患者的功效和安全数据。 CCL-20和CXCL-8的过表达可能代表缺乏对免疫疗法反应的生物标志物。
Abstract
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.