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

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 CD8+T cell infiltration in OCCC is cru...

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Main Authors: Mengdi Fu, Huimei Zhou, Jiaxin Yang, Dongyan Cao, Zhen Yuan
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-89270-z
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author Mengdi Fu
Huimei Zhou
Jiaxin Yang
Dongyan Cao
Zhen Yuan
author_facet Mengdi Fu
Huimei Zhou
Jiaxin Yang
Dongyan Cao
Zhen Yuan
author_sort Mengdi Fu
collection DOAJ
description 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 CD8+T 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/mm2 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.
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spelling doaj-art-1126c0465e2946d29c7264fb0a0eb4ad2025-02-09T12:35:44ZengNature PortfolioScientific Reports2045-23222025-02-0115111110.1038/s41598-025-89270-zInfiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinomaMengdi Fu0Huimei Zhou1Jiaxin Yang2Dongyan Cao3Zhen Yuan4Department 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 CollegeDepartment 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 CollegeDepartment 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 CollegeDepartment 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 CollegeDepartment 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 CollegeAbstract 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 CD8+T 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/mm2 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.https://doi.org/10.1038/s41598-025-89270-zPD-1PD-L1CD8+ T-cellsProgression-free survivalOCCC
spellingShingle Mengdi Fu
Huimei Zhou
Jiaxin Yang
Dongyan Cao
Zhen Yuan
Infiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma
Scientific Reports
PD-1
PD-L1
CD8+ T-cells
Progression-free survival
OCCC
title Infiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma
title_full Infiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma
title_fullStr Infiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma
title_full_unstemmed Infiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma
title_short Infiltration of CD8+ cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma
title_sort infiltration of cd8 cytotoxic t cells and expression of pd 1 and pd l1 in ovarian clear cell carcinoma
topic PD-1
PD-L1
CD8+ T-cells
Progression-free survival
OCCC
url https://doi.org/10.1038/s41598-025-89270-z
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