Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma

Abstract Background Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are u...

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Main Authors: Jie Hu, Takeshi Toyozumi, Kentaro Murakami, Satoshi Endo, Yasunori Matsumoto, Ryota Otsuka, Tadashi Shiraishi, Shinichiro Iida, Hiroki Morishita, Tenshi Makiyama, Yuri Nishioka, Masaya Uesato, Koichi Hayano, Akira Nakano, Hisahiro Matsubara
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70179
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author Jie Hu
Takeshi Toyozumi
Kentaro Murakami
Satoshi Endo
Yasunori Matsumoto
Ryota Otsuka
Tadashi Shiraishi
Shinichiro Iida
Hiroki Morishita
Tenshi Makiyama
Yuri Nishioka
Masaya Uesato
Koichi Hayano
Akira Nakano
Hisahiro Matsubara
author_facet Jie Hu
Takeshi Toyozumi
Kentaro Murakami
Satoshi Endo
Yasunori Matsumoto
Ryota Otsuka
Tadashi Shiraishi
Shinichiro Iida
Hiroki Morishita
Tenshi Makiyama
Yuri Nishioka
Masaya Uesato
Koichi Hayano
Akira Nakano
Hisahiro Matsubara
author_sort Jie Hu
collection DOAJ
description Abstract Background Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD‐L1 expression and TILs in ESCC. Methods Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. Results PD‐L1 was expressed in tumor cells (PD‐L1 TC). PD‐L1 TIIC and PD‐L1 TC affected the biological behavior of TC. The positive expression rate of PD‐L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan–Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD‐L1 TC‐positive expression, which promote ESCC progression and metastasis. Conclusion Tumor depth, CD8, and PD‐L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune‐related factors is beneficial for stratifying patient survival risk.
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spelling doaj-art-b02b9147a0c34d9f96d7bc5c64ddbded2025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70179Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinomaJie Hu0Takeshi Toyozumi1Kentaro Murakami2Satoshi Endo3Yasunori Matsumoto4Ryota Otsuka5Tadashi Shiraishi6Shinichiro Iida7Hiroki Morishita8Tenshi Makiyama9Yuri Nishioka10Masaya Uesato11Koichi Hayano12Akira Nakano13Hisahiro Matsubara14Department of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanDepartment of Frontier Surgery Graduate School of Medicine, Chiba University Chiba JapanAbstract Background Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD‐L1 expression and TILs in ESCC. Methods Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. Results PD‐L1 was expressed in tumor cells (PD‐L1 TC). PD‐L1 TIIC and PD‐L1 TC affected the biological behavior of TC. The positive expression rate of PD‐L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan–Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD‐L1 TC‐positive expression, which promote ESCC progression and metastasis. Conclusion Tumor depth, CD8, and PD‐L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune‐related factors is beneficial for stratifying patient survival risk.https://doi.org/10.1002/cam4.70179esophageal squamous cell carcinomaPD‐L1regulatory T cellstumor microenvironmenttumor‐infiltrating lymphocytes
spellingShingle Jie Hu
Takeshi Toyozumi
Kentaro Murakami
Satoshi Endo
Yasunori Matsumoto
Ryota Otsuka
Tadashi Shiraishi
Shinichiro Iida
Hiroki Morishita
Tenshi Makiyama
Yuri Nishioka
Masaya Uesato
Koichi Hayano
Akira Nakano
Hisahiro Matsubara
Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma
Cancer Medicine
esophageal squamous cell carcinoma
PD‐L1
regulatory T cells
tumor microenvironment
tumor‐infiltrating lymphocytes
title Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma
title_full Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma
title_fullStr Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma
title_full_unstemmed Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma
title_short Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma
title_sort prognostic value of tumor infiltrating lymphocytes and pd l1 expression in esophageal squamous cell carcinoma
topic esophageal squamous cell carcinoma
PD‐L1
regulatory T cells
tumor microenvironment
tumor‐infiltrating lymphocytes
url https://doi.org/10.1002/cam4.70179
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