Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia
Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia.
J Clin Pathol. 2024 Apr 18;77(5):343-351. doi: 10.1136/jcp-2022-208615.
Despite efficacy of anti-PD-1 blockade in treatment of metastatic melanoma (MM), many patients achieve rapid disease progression (DP). Therefore, the aim of this study is to better define biomarkers for DP by analysing levels of circulating cytokines TGF-β, IFN-γ, IL-6, IL-8 and IL-10 in MM patients prior to anti-PD-1 therapy.
Cytokine levels were evaluated before therapy with pembrolizumab in peripheral blood of BRAF wild-type (wt) MM patients by ELISA method.
In this study, we give pretherapy levels for circulating TGF-β, IFN-γ, IL-6, IL-8 and IL-10 in BRAFwt MM patients and analyse them according to metastasis stage (M1a+M1 b, M1c, M1d groups), lactate dehydrogenase (LDH) level and occurrence of DP. Increased IL-6 level was found in M1d group (central nervous system metastasis), while LDH+patients (LDH ≥460 IU/L) have increased IL-6 and IL-8 values that correlate with LDH level. Also, IL-6 correlates with C reactive protein values. Furthermore, patients with DP have significantly higher IL-6 level compared with non-DP patients. Conversely, the other analysed cytokines are similar in investigated groups of MM patients. By receiver operating characteristics curve analysis, pretherapy IL-6 level was found to be a biomarker for the occurrence of DP with cut-off value of 3.02 pg/mL. Patients in M1d stage are prevalent in the group with IL-6 ≥3.02 pg/mL that is characterised with reduced progression-free survival and higher pretherapy IL-8 and LDH.
The evidence in this study implies that baseline IL-6 could be a biomarker of DP and poor prognosis in BRAFwt MM patients treated with pembrolizumab.
尽管抗 PD-1 阻断在治疗转移性黑色素瘤 (MM) 方面具有疗效，但许多患者会出现快速疾病进展 (DP)。因此，本研究旨在通过分析抗 PD-1 治疗前 MM 患者循环细胞因子 TGF-β、IFN-γ、IL-6、IL-8 和 IL-10 的水平，更好地定义 DP 的生物标志物。
通过 ELISA 法检测 BRAF 野生型 (wt) MM 患者接受 pembrolizumab 治疗前外周血中细胞因子的水平。
在这项研究中，我们提供了 BRAFwt MM 患者治疗前循环 TGF-β、IFN-γ、IL-6、IL-8 和 IL-10 的水平，并根据转移阶段 (M1a+M1b、M1c、M1d 组)、乳酸脱氢酶 (LDH) 水平和 DP 的发生对其进行了分析。在 M1d 组（中枢神经系统转移）中发现 IL-6 水平升高，而 LDH+患者（LDH≥460IU/L）的 IL-6 和 IL-8 值升高，与 LDH 水平相关。此外，IL-6 与 C 反应蛋白值相关。此外，与非 DP 患者相比，DP 患者的 IL-6 水平显著升高。相反，在研究的 MM 患者组中，其他分析的细胞因子相似。通过接受者操作特征曲线分析，发现治疗前 IL-6 水平是 DP 发生的生物标志物，截断值为 3.02pg/mL。IL-6≥3.02pg/mL 患者中 M1d 期更为常见，其特点是无进展生存期缩短，治疗前 IL-8 和 LDH 升高。
本研究的证据表明，基线 IL-6 可能是 BRAFwt MM 患者接受 pembrolizumab 治疗时 DP 和不良预后的生物标志物。
