Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Front Immunol. 2024 Jul 11;15:1401097. doi: 10.3389/fimmu.2024.1401097. eCollection 2024.
The aim of this study was to assess the role of sPD-L1 and sPD-1 as potential biomarkers in prostate cancer (PCa). The association of the values of these soluble proteins were correlated to the clinical data: stage of disease, Gleason score, biochemical recurrence etc. For a comprehensive study, the relationship between sPD-L1 and sPD-1 and circulating immune cells was further investigated.
A total of 88 patients with pT2 and pT3 PCa diagnosis and 41 heathy men were enrolled. Soluble sPD-L1 and sPD-1 levels were measured in plasma by ELISA method. Immunophenotyping was performed by flow cytometry analysis.
Our study's findings demonstrate that PCa patients had higher levels of circulating sPD-L1 and sPD-1 comparing to healthy controls (p < 0.001). We found a statistically significant (p < 0.05) relationship between improved progression free survival and lower initial sPD-L1 values. Furthermore, patients with a lower sPD-1/sPD-L1 ratio were associated with a higher probability of disease progression (p < 0.05). Additionally, a significant (p < 0.05) association was discovered between higher Gleason scores and elevated preoperative sPD-L1 levels and between sPD-1 and advanced stage of disease (p < 0.05). A strong correlation (p < 0.05), between immunosuppressive CD4+CD25+FoxP3+ regulatory T cells and baseline sPD-L1 was observed in patients with unfavorable postoperative course of the disease, supporting the idea that these elements influence each other in cancer progression. In addition to the postoperative drop in circulating PD-L1, the inverse relationship (p < 0.05), between the percentage of M-MDSC and sPD-L1 in patients with BCR suggests that M-MDSC is not a source of sPD-L1 in PCa patients.
Our findings suggest the potential of sPD-L1 as a promising prognostic marker in prostate cancer.
本研究旨在评估 sPD-L1 和 sPD-1 作为前列腺癌(PCa)潜在生物标志物的作用。这些可溶性蛋白值与临床数据(疾病分期、Gleason 评分、生化复发等)的相关性进行了分析。为了进行全面的研究,进一步研究了 sPD-L1 和 sPD-1 与循环免疫细胞之间的关系。
共纳入 88 例 pT2 和 pT3 PCa 诊断患者和 41 名健康男性。采用 ELISA 法检测血浆中可溶性 sPD-L1 和 sPD-1 水平。采用流式细胞术分析进行免疫表型分析。
本研究发现,与健康对照组相比,PCa 患者的循环 sPD-L1 和 sPD-1 水平更高(p<0.001)。我们发现,无进展生存期改善与初始 sPD-L1 值降低之间存在统计学显著关系(p<0.05)。此外,sPD-1/sPD-L1 比值较低的患者疾病进展的概率更高(p<0.05)。此外,还发现术前 sPD-L1 水平与较高的 Gleason 评分和晚期疾病之间存在显著相关性(p<0.05),sPD-1 与晚期疾病之间也存在相关性(p<0.05)。在术后疾病进程不利的患者中,观察到免疫抑制性 CD4+CD25+FoxP3+调节性 T 细胞与基线 sPD-L1 之间存在强烈相关性(p<0.05),支持这些因素在癌症进展中相互影响的观点。除了循环 PD-L1 术后下降外,BCR 患者中 M-MDSC 与 sPD-L1 之间的反比关系(p<0.05)表明 M-MDSC 不是 PCa 患者 sPD-L1 的来源。
我们的研究结果表明,sPD-L1 作为前列腺癌有前途的预后标志物具有潜力。