Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer
Gastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4 and IFN-γ in the tumor and regional lymph node (LN) of patients with GC and compared it with...
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/709 |
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| author | Tomislav Ivanović Dorotea Božić Benjamin Benzon Vesna Čapkun Katarina Vukojević Merica Glavina Durdov |
| author_facet | Tomislav Ivanović Dorotea Božić Benjamin Benzon Vesna Čapkun Katarina Vukojević Merica Glavina Durdov |
| author_sort | Tomislav Ivanović |
| collection | DOAJ |
| description | Gastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4 and IFN-γ in the tumor and regional lymph node (LN) of patients with GC and compared it with clinical and pathological data. Paraffin blocks were collected from 97 patients undergoing gastrectomy/lymphadenectomy for GC. Double immunohistochemistry was performed for CD8 and PD-L1 and double immunofluorescence for CTLA-4 and IFN-γ. Statistical significance was set at <i>p</i> < 0.05. PD-L1 expression in tumor cells was associated with intestinal GC type (<i>p</i> = 0.046), the density of macrophages and CD8 + T cells (<i>p</i> < 0.001, both). The median number of CD8+ T cells was higher in PD-L1-positive than in -negative tumors. A cut-off of 28.5 CD8 + T cells in one high-magnification field predicted PD-L1-positive tumors (AUROC 0.797, sensitivity 74.2%, specificity 77.3%). IFN-γ expression in tumor cells was found in 37 GCs and was positively associated with CTLA4<sup>+</sup> lymphocytes in the LN (<i>p</i> = 0.027) and CTLA4<sup>+</sup>/IFN-γ+ in tumors and the LN (all <i>p</i> < 0.001). The median overall survival (OS) was 17 months. In the group of deceased patients, IFN-γ expression in metastases correlated with lower OS (RHO = −0.314, <i>p</i> = 0.008). PD-L1 expression in tumor cells correlated with CD8 + T cells and macrophages in the TME and IFN-γ expression with suppressive CTLA4<sup>+</sup>/IFNγ+ immune cells in the TME and LN. |
| first_indexed | 2024-03-11T06:54:11Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:54:11Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-1c33257a554a4b13b66832661649b4ec2023-11-17T09:44:27ZengMDPI AGBiomedicines2227-90592023-02-0111370910.3390/biomedicines11030709Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric CancerTomislav Ivanović0Dorotea Božić1Benjamin Benzon2Vesna Čapkun3Katarina Vukojević4Merica Glavina Durdov5Surgery Department, University Hospital in Split, Spinčićeva 1, 21000 Split, CroatiaDepartment of Internal Medicine, University Hospital in Split, Spinciceva 1, 21000 Split, CroatiaDepartment of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, CroatiaDepartment of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, CroatiaDepartment of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, CroatiaDepartment of Pathology, Legal Medicine and Cytology, University Hospital in Split, 21000 Split, CroatiaGastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4 and IFN-γ in the tumor and regional lymph node (LN) of patients with GC and compared it with clinical and pathological data. Paraffin blocks were collected from 97 patients undergoing gastrectomy/lymphadenectomy for GC. Double immunohistochemistry was performed for CD8 and PD-L1 and double immunofluorescence for CTLA-4 and IFN-γ. Statistical significance was set at <i>p</i> < 0.05. PD-L1 expression in tumor cells was associated with intestinal GC type (<i>p</i> = 0.046), the density of macrophages and CD8 + T cells (<i>p</i> < 0.001, both). The median number of CD8+ T cells was higher in PD-L1-positive than in -negative tumors. A cut-off of 28.5 CD8 + T cells in one high-magnification field predicted PD-L1-positive tumors (AUROC 0.797, sensitivity 74.2%, specificity 77.3%). IFN-γ expression in tumor cells was found in 37 GCs and was positively associated with CTLA4<sup>+</sup> lymphocytes in the LN (<i>p</i> = 0.027) and CTLA4<sup>+</sup>/IFN-γ+ in tumors and the LN (all <i>p</i> < 0.001). The median overall survival (OS) was 17 months. In the group of deceased patients, IFN-γ expression in metastases correlated with lower OS (RHO = −0.314, <i>p</i> = 0.008). PD-L1 expression in tumor cells correlated with CD8 + T cells and macrophages in the TME and IFN-γ expression with suppressive CTLA4<sup>+</sup>/IFNγ+ immune cells in the TME and LN.https://www.mdpi.com/2227-9059/11/3/709gastric cancertumor immune microenvironmentPD-L1CTLA-4IFN-γ |
| spellingShingle | Tomislav Ivanović Dorotea Božić Benjamin Benzon Vesna Čapkun Katarina Vukojević Merica Glavina Durdov Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer Biomedicines gastric cancer tumor immune microenvironment PD-L1 CTLA-4 IFN-γ |
| title | Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer |
| title_full | Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer |
| title_fullStr | Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer |
| title_full_unstemmed | Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer |
| title_short | Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer |
| title_sort | histological type cytotoxic t cells and macrophages in the tumor microenvironment affect the pd l1 status of gastric cancer |
| topic | gastric cancer tumor immune microenvironment PD-L1 CTLA-4 IFN-γ |
| url | https://www.mdpi.com/2227-9059/11/3/709 |
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