Kött Julian, Hoehne Inka Lilott, Heidrich Isabel, Zimmermann Noah, Reese Kim-Lea, Zell Tim, Geidel Glenn, Rünger Alessandra, Schneider Stefan W, Pantel Klaus, Smit Daniel J, Gebhardt Christoffer
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Cancers (Basel). 2024 Apr 29;16(9):1737. doi: 10.3390/cancers16091737.
Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression.
In this prospective study, we analyzed the serum C-C motif chemokine ligand 20 (CCL20) concentration using an enzyme-linked immunosorbent assay. Blood was obtained at baseline before the initiation of immunotherapy with anti-PD-1 monotherapy or Nivolumab and Ipilimumab in advanced melanoma patients (stages III and IV) enrolled at the University Medical Center Hamburg-Eppendorf. The CCL20 levels were correlated with clinico-pathological parameters and disease-related outcomes.
An increased C-C motif chemokine ligand 20 (CCL20) concentration (≥0.34 pg/mL) at baseline was associated with a significantly impaired progression-free survival (PFS) in the high-CCL20 group (3 months (95% CI: 2-6 months) vs. 11 months (95% CI: 6-26 months)) ( = 0.0033) and could be identified as an independent negative prognostic factor for PFS in univariate (Hazard Ratio (HR): 1.98, 95% CI 1.25-3.12, = 0.004) and multivariate (HR: 1.99, 95% CI 1.21-3.29, = 0.007) Cox regression analysis, which was associated with a higher risk than S100 (HR: 1.74). Moreover, high CCL20 levels were associated with impaired overall survival (median OS not reached for low-CCL20 group, = 0.042) with an HR of 1.85 (95% CI 1.02-3.37, = 0.043) in univariate analysis similar to the established prognostic marker S100 (HR: 1.99, 95% CI: 1.02-3.88, = 0.043).
CCL20 may represent a novel blood-based biomarker for the prediction of resistance to immunotherapy that can be used in combination with established strong clinical predictors (e.g., ECOG performance score) and laboratory markers (e.g., S100) in advanced melanoma patients. Future prospective randomized trials are needed to establish CCL20 as a liquid biopsy-based biomarker in advanced melanoma.
免疫检查点抑制疗法彻底改变了黑色素瘤的治疗方式，但许多患者表现出原发性或继发性耐药。因此，迫切需要生物标志物来在治疗开始前预测反应并监测疾病进展。
在这项前瞻性研究中，我们使用酶联免疫吸附测定法分析血清C-C基序趋化因子配体20（CCL20）浓度。在汉堡-埃彭多夫大学医学中心招募的晚期黑色素瘤患者（III期和IV期）中，于使用抗PD-1单药疗法或纳武单抗和伊匹木单抗进行免疫治疗开始前的基线期采集血液。CCL20水平与临床病理参数及疾病相关结局相关。
基线时C-C基序趋化因子配体20（CCL20）浓度升高（≥0.34 pg/mL）与高CCL20组无进展生存期（PFS）显著受损相关（3个月（95%CI：2 - 6个月）对11个月（95%CI：6 - 26个月））（P = 0.0033），并且在单因素（风险比（HR）：1.98，95%CI 1.25 - 3.12，P = 0.004）和多因素（HR：1.99，95%CI 1.21 - 3.29，P = 0.007）Cox回归分析中可被确定为PFS的独立阴性预后因素，其风险高于S100（HR：1.74）。此外，高CCL2水平与总生存期受损相关（低CCL20组未达到中位总生存期，P = 0.042），单因素分析中的HR为1.85（95%CI 1.02 - 3.37，P = 0.043），与已确立的预后标志物S100相似（HR：1.99，95%CI：1.02 - 3.88，P = 0.043）。
CCL20可能代表一种用于预测免疫治疗耐药性的新型血液生物标志物，可与晚期黑色素瘤患者已确立的强大临床预测指标（如东部肿瘤协作组体能状态评分）和实验室标志物（如S100）联合使用。未来需要进行前瞻性随机试验，以将CCL20确立为晚期黑色素瘤基于液体活检的生物标志物。
