Kontomanolis Emmanuel, Koutras Antonios, Mitrakas Achilleas G, Trypsianis Grigorios, Nikolettos Konstantinos, Tsikouras Panagiotis, Nikolettos Nikolaos, Giatromanolaki Alexandra, Koukourakis Michael
Department of Obstetrics/Gynecology, Democritus University of Thrace, Alexandroupolis, Greece.
Department of Radiotherapy and Oncology, Democritus University of Thrace, Alexandroupolis, Greece.
Anticancer Res. 2024 Dec;44(12):5525-5530. doi: 10.21873/anticanres.17378.
BACKGROUND/AIM: The prognostic role of tissue PD-L1 expression in endometrial cancer (EC) remains controversial. Moreover, its value in guiding anti-PD1/PD-L1 immunotherapy is questionable. The eventual role of soluble PD-L1 (sPD-L1), released by cancer tissue and circulating immune cells, is largely unexplored.
In this pilot study, we investigated the expression of PD-L1 in cancer cells and tumor stroma infiltrating inflammatory cells (TIICs), in parallel with sPD-L1 levels in the plasma of 19 patients with early-stage endometrioid EC, before and after hysterectomy.
Cancer cell membrane staining was noted in 5/19 (26.3%) cases (range=1-5%; median 1% of the cancer cell population). IICs showed positive reactivity in 14/19 (73.7%) cases. sPD-L1 plasma levels ranged from 53-408 pg/ml and 113-557 pg/ml, respectively, in the plasma of patients before and after hysterectomy (p=0.01). High PD-L1 expression by IIC was marginally associated with a high histology grade (p=0.08). High sPD-L1 levels before surgery were significantly associated with ICC PD-L1 expression (p=0.0007), high histology grade (p=0.04), and marginally with T2-stage (p=0.08).
sPD-L1 is easily detectable in the plasma of EC patients and may be associated with aggressive clinical features and PD-L1-expressing immune cells infiltrating the tumor stroma. sPD-L1 plasma levels in EC patients undergoing immunotherapy can be further tested as a biomarker for therapeutic stratification.
背景/目的：组织程序性死亡配体1（PD-L1）表达在子宫内膜癌（EC）中的预后作用仍存在争议。此外，其在指导抗程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）免疫治疗方面的价值也存在疑问。由癌组织和循环免疫细胞释放的可溶性PD-L1（sPD-L1）的最终作用在很大程度上尚未得到探索。
在这项前瞻性研究中，我们调查了19例早期子宫内膜样EC患者在子宫切除术前和术后癌细胞及肿瘤基质浸润炎性细胞（TIICs）中PD-L1的表达情况，并同时检测了其血浆中sPD-L1水平。
19例患者中有5例（26.3%）癌细胞膜染色呈阳性（范围为1%-5%；癌细胞群体中位数为1%）。19例患者中有14例（73.7%）TIICs呈阳性反应。子宫切除术前和术后患者血浆中sPD-L1水平分别为53-408 pg/ml和113-557 pg/ml（p=0.01）。TIICs中高PD-L1表达与高组织学分级有微弱关联（p=0.08）。术前高sPD-L1水平与肿瘤细胞PD-L1表达显著相关（p=0.0007），与高组织学分级相关（p=0.04），与T2期有微弱关联（p=0.08）。
sPD-L1在EC患者血浆中易于检测到，可能与侵袭性临床特征以及肿瘤基质中表达PD-L1的免疫细胞浸润有关。接受免疫治疗的EC患者血浆中sPD-L1水平可作为治疗分层的生物标志物进行进一步检测。
