Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma
The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of stainin...
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MDPI AG
2024-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/6/1135 |
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| author | Tomohiro Murakami Eisuke Booka Satoru Furuhashi Yuki Sakai Kenichi Sekimori Ryoma Haneda Mayu Fujihiro Tomohiro Matsumoto Yoshifumi Morita Hirotoshi Kikuchi Yoshihiro Hiramatsu Satoshi Baba Hiroya Takeuchi |
| author_facet | Tomohiro Murakami Eisuke Booka Satoru Furuhashi Yuki Sakai Kenichi Sekimori Ryoma Haneda Mayu Fujihiro Tomohiro Matsumoto Yoshifumi Morita Hirotoshi Kikuchi Yoshihiro Hiramatsu Satoshi Baba Hiroya Takeuchi |
| author_sort | Tomohiro Murakami |
| collection | DOAJ |
| description | The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan–Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, <i>p</i> = 0.007; HR = 0.54, <i>p</i> = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1’s contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response. |
| first_indexed | 2024-04-24T18:27:55Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-24T18:27:55Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-658cef21b56e4c0f88098a0ab046e32c2024-03-27T13:29:55ZengMDPI AGCancers2072-66942024-03-01166113510.3390/cancers16061135Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell CarcinomaTomohiro Murakami0Eisuke Booka1Satoru Furuhashi2Yuki Sakai3Kenichi Sekimori4Ryoma Haneda5Mayu Fujihiro6Tomohiro Matsumoto7Yoshifumi Morita8Hirotoshi Kikuchi9Yoshihiro Hiramatsu10Satoshi Baba11Hiroya Takeuchi12Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Diagnostic Pathology; Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Diagnostic Pathology; Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanDepartment of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu City 431-3192, Shizuoka, JapanThe assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan–Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, <i>p</i> = 0.007; HR = 0.54, <i>p</i> = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1’s contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.https://www.mdpi.com/2072-6694/16/6/1135esophageal squamous cell carcinomaPD-L1 expressionimmunohistochemistryprognostic factorchemotherapy response |
| spellingShingle | Tomohiro Murakami Eisuke Booka Satoru Furuhashi Yuki Sakai Kenichi Sekimori Ryoma Haneda Mayu Fujihiro Tomohiro Matsumoto Yoshifumi Morita Hirotoshi Kikuchi Yoshihiro Hiramatsu Satoshi Baba Hiroya Takeuchi Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma Cancers esophageal squamous cell carcinoma PD-L1 expression immunohistochemistry prognostic factor chemotherapy response |
| title | Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma |
| title_full | Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma |
| title_fullStr | Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma |
| title_full_unstemmed | Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma |
| title_short | Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma |
| title_sort | contrasting roles of programmed death ligand 1 expression in tumor and stroma in prognosis of esophageal squamous cell carcinoma |
| topic | esophageal squamous cell carcinoma PD-L1 expression immunohistochemistry prognostic factor chemotherapy response |
| url | https://www.mdpi.com/2072-6694/16/6/1135 |
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