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CD8 细胞毒性 T 细胞浸润及 PD - 1 和 PD - L1 在卵巢透明细胞癌中的表达

Infiltration of CD8 cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma.

作者信息

Fu Mengdi, Zhou Huimei, Yang Jiaxin, Cao Dongyan, Yuan Zhen

机构信息

Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China.

出版信息

Sci Rep. 2025 Feb 8;15(1):4716. doi: 10.1038/s41598-025-89270-z.

Abstract

Ovarian clear cell carcinoma (OCCC) is resistant to chemotherapy, with limited treatment options for advanced and recurrent disease. The prevalence of OCCC differs by region. Assessing the expression of programmed cell death ligand 1 (PD-L1), PD-1, and CD8T cell infiltration in OCCC is crucial, as their correlation with patient survival may provide valuable prognostic insights. We collected data from 36 samples from 18 OCCC patients, including 18 pairs of tumors and adjacent nonneoplastic samples. The optimized multiplex immunofluorescence technique was used to stain paraffin sections for immune factors related to the immune microenvironment of OCCC and clinical prognosis. The expression of PDL1 and PD1 in the tumor cells and tumor stromal cells was not significantly correlated with prognosis. Professional quantitative pathological analysis software was used to count the CD8 cytotoxic T-cells in tumor regions and adjacent nonneoplastic regions in postoperative specimens. There were more CD8 cytotoxic T-cells in the adjacent nonneoplastic areas than in the tumor tissue samples (p < 0.001). Further analysis revealed that a difference in cell density between CD8 non-tumor-infiltrating lymphocytes (NTILs) and CD8 tumor-infiltrating lymphocytes (TILs) exceeding 70 cells/mm was associated with poorer progression-free survival (PFS) (p = 0.042). In adjacent nonneoplastic regions, worse PFS was significantly observed in patients with high CD8 T-cell expression in both total and stromal cells than those with low expression (p = 0.012 vs p = 0.007). The presence of CD8 T-cells had significant potential for predicting the prognosis of patients with OCCC, which lays a foundation for the development of biomarkers for immune checkpoint blockade treatment response in OCCC patients.

摘要

卵巢透明细胞癌(OCCC)对化疗耐药,晚期和复发性疾病的治疗选择有限。OCCC的患病率因地区而异。评估程序性细胞死亡配体1(PD-L1)、PD-1和CD8 T细胞浸润在OCCC中的表达至关重要,因为它们与患者生存的相关性可能提供有价值的预后见解。我们收集了18例OCCC患者的36个样本数据,包括18对肿瘤和相邻的非肿瘤样本。采用优化的多重免疫荧光技术对石蜡切片进行染色,以检测与OCCC免疫微环境和临床预后相关的免疫因子。肿瘤细胞和肿瘤基质细胞中PDL1和PD1的表达与预后无显著相关性。使用专业的定量病理分析软件对术后标本肿瘤区域和相邻非肿瘤区域的CD8细胞毒性T细胞进行计数。相邻非肿瘤区域的CD8细胞毒性T细胞比肿瘤组织样本中的更多(p < 0.001)。进一步分析显示,CD8非肿瘤浸润淋巴细胞(NTILs)和CD8肿瘤浸润淋巴细胞(TILs)之间的细胞密度差异超过70个细胞/mm与无进展生存期(PFS)较差相关(p = 0.042)。在相邻非肿瘤区域,总细胞和基质细胞中CD8 T细胞高表达的患者的PFS明显比低表达患者差(p = 0.012 vs p = 0.007)。CD8 T细胞的存在对预测OCCC患者的预后具有显著潜力,这为开发OCCC患者免疫检查点阻断治疗反应的生物标志物奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a5/11807128/fd1205f7add7/41598_2025_89270_Fig1_HTML.jpg

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