School of Medicine, University of Zagreb, Zagreb, Croatia.
Department of Urology, University Hospital Centre Sisters of Charity, Zagreb, Croatia.
Biomol Biomed. 2024 Oct 17;24(6):1751-1760. doi: 10.17305/bb.2024.10745.
Spontaneous regression of testicular germ cell tumors is a well-known phenomenon; however, the precise mechanisms of spontaneous regression are still unknown. Our study aimed to investigate programmed death-ligand 1 (PD-L1) expression in spontaneously regressed testicular germ cell tumors, exploring the link between the immune response and spontaneous regression. From a sample of 356 testicular germ cell tumors, we singled out 5 completely regressed and 6 partially regressed tumors. In four out of six cases with partial regression, a residual seminoma component was found, while in the remaining two cases, an embryonal carcinoma component was found. Comparisons were made with 20 pure seminomas and 20 mixed germ cell tumors (MGCTs). A semiquantitative immunohistochemical analysis of PD-L1 expression in tumor cells and intra/peritumoral lymphocytes was performed. There was no PD-L1 expression in tumors with complete regression. All partially regressed tumors showed expression in intra/peritumoral lymphocytes within the tumor remnants. Expression was significantly more frequent in pure seminomas compared to MGCTs (P = 0.004). A positive correlation was demonstrated between the seminoma component and the proportion of PD-L1 positive lymphocytes, with a Kendall's Tau-b coefficient of 0.626 (P < 0.001). Tumor cells showed PD-L1 expression in three MGCTs within the embryonal carcinoma component. Our results support an immunological mechanism of spontaneous tumor regression, with the strongest potential in testicular tumors containing seminoma components. However, further research is necessary to determine the role of PD-L1 ligand more precisely in the microenvironment of spontaneously regressed tumors.
睾丸生殖细胞肿瘤的自发消退是一种众所周知的现象;然而,自发消退的确切机制仍不清楚。我们的研究旨在探讨程序性死亡配体 1(PD-L1)在自发消退的睾丸生殖细胞肿瘤中的表达,探索免疫反应与自发消退之间的联系。在 356 例睾丸生殖细胞肿瘤的样本中,我们单独挑选了 5 例完全消退和 6 例部分消退的肿瘤。在 6 例部分消退的病例中,有 4 例发现残留的精原细胞瘤成分,而在其余 2 例中发现胚胎癌成分。将其与 20 例单纯精原细胞瘤和 20 例混合生殖细胞瘤(MGCT)进行比较。对肿瘤细胞和肿瘤内/周围淋巴细胞中的 PD-L1 表达进行半定量免疫组织化学分析。完全消退的肿瘤均无 PD-L1 表达。所有部分消退的肿瘤在肿瘤残迹内的肿瘤内/周围淋巴细胞中均显示表达。与 MGCT 相比,单纯精原细胞瘤的表达明显更频繁(P=0.004)。在单纯精原细胞瘤中,精原细胞瘤成分与 PD-L1 阳性淋巴细胞的比例之间表现出正相关,Kendall's Tau-b 系数为 0.626(P<0.001)。在胚胎癌成分中的 3 例 MGCT 中,肿瘤细胞显示出 PD-L1 表达。我们的研究结果支持自发肿瘤消退的免疫学机制,在含有精原细胞瘤成分的睾丸肿瘤中具有最大的潜力。然而,需要进一步的研究来更准确地确定 PD-L1 配体在自发消退肿瘤的微环境中的作用。