C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma
BackgroundC-reactive protein (CRP) is a widely used marker of systemic inflammation and predicts poor clinical outcomes in patients with hepatocellular carcinoma (HCC); however, its significance in the local immune response at the tumor site is not clear.MethodsSerum CRP levels of 329 HCC patients w...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.774823/full |
| _version_ | 1797652634894598144 |
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| author | Yongchun Wang Zhixiong Li Zhijie Huang Xingjuan Yu Limin Zheng Limin Zheng Jing Xu |
| author_facet | Yongchun Wang Zhixiong Li Zhijie Huang Xingjuan Yu Limin Zheng Limin Zheng Jing Xu |
| author_sort | Yongchun Wang |
| collection | DOAJ |
| description | BackgroundC-reactive protein (CRP) is a widely used marker of systemic inflammation and predicts poor clinical outcomes in patients with hepatocellular carcinoma (HCC); however, its significance in the local immune response at the tumor site is not clear.MethodsSerum CRP levels of 329 HCC patients were detected before resection. Paired paraffin-embedded tumor samples were used to quantify immune cell populations, such as CD11b+ myeloid cells, CD68+ macrophages (Mφs), CD15+ neutrophils, CD8+ T cells, and CD206+, CD204+, CD163+ and CD169+ Mφs, by immunohistochemistry. Enrichment scores for 34 types of immune cells based on transcriptome data from 24 HCC samples were calculated by xCell. Overall survival of patients was analyzed using the Kaplan-Meier method.ResultsSerum CRP levels were correlated with liver functions and tumor stages in patients with HCC. The densities of CD68+ tumor-associated macrophages (TAMs) and CD15+ tumor-associated neutrophils (TANs) were significantly higher in patients with elevated serum CRP levels than in those with low CRP levels (both p < 0.0001). Further analysis of TAM subtypes revealed that serum CRP levels were associated with CD204+ and CD163+ Mφ densities (p < 0.0001 and p = 0.0003, respectively). Moreover, transcriptome data showed that CRP expression was associated with the expression of myeloid cell infiltration-related genes in HCC tumors. The combination of serum CRP with TAMs or TANs in both the nontumor and intratumor regions could represent a powerful criterion for predicting patient prognoses.ConclusionSerum CRP could serve as an indicator of an immunosuppressive TME in HCC, which could be of potential clinical application for treatment strategies targeting the TME. |
| first_indexed | 2024-03-11T16:32:49Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-11T16:32:49Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-046be3929ac54485b95da5ed901d54d02023-10-23T21:40:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.774823774823C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular CarcinomaYongchun Wang0Zhixiong Li1Zhijie Huang2Xingjuan Yu3Limin Zheng4Limin Zheng5Jing Xu6Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaMinistry Of Education (MOE) Key Laboratory of Gene Function and Regulation, School of Life Science, Sun Yat-sen University, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBackgroundC-reactive protein (CRP) is a widely used marker of systemic inflammation and predicts poor clinical outcomes in patients with hepatocellular carcinoma (HCC); however, its significance in the local immune response at the tumor site is not clear.MethodsSerum CRP levels of 329 HCC patients were detected before resection. Paired paraffin-embedded tumor samples were used to quantify immune cell populations, such as CD11b+ myeloid cells, CD68+ macrophages (Mφs), CD15+ neutrophils, CD8+ T cells, and CD206+, CD204+, CD163+ and CD169+ Mφs, by immunohistochemistry. Enrichment scores for 34 types of immune cells based on transcriptome data from 24 HCC samples were calculated by xCell. Overall survival of patients was analyzed using the Kaplan-Meier method.ResultsSerum CRP levels were correlated with liver functions and tumor stages in patients with HCC. The densities of CD68+ tumor-associated macrophages (TAMs) and CD15+ tumor-associated neutrophils (TANs) were significantly higher in patients with elevated serum CRP levels than in those with low CRP levels (both p < 0.0001). Further analysis of TAM subtypes revealed that serum CRP levels were associated with CD204+ and CD163+ Mφ densities (p < 0.0001 and p = 0.0003, respectively). Moreover, transcriptome data showed that CRP expression was associated with the expression of myeloid cell infiltration-related genes in HCC tumors. The combination of serum CRP with TAMs or TANs in both the nontumor and intratumor regions could represent a powerful criterion for predicting patient prognoses.ConclusionSerum CRP could serve as an indicator of an immunosuppressive TME in HCC, which could be of potential clinical application for treatment strategies targeting the TME.https://www.frontiersin.org/articles/10.3389/fonc.2021.774823/fullCRPHCCimmune microenviromenttumor associated macrophagetumor associated neutrophil |
| spellingShingle | Yongchun Wang Zhixiong Li Zhijie Huang Xingjuan Yu Limin Zheng Limin Zheng Jing Xu C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma Frontiers in Oncology CRP HCC immune microenviroment tumor associated macrophage tumor associated neutrophil |
| title | C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma |
| title_full | C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma |
| title_fullStr | C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma |
| title_full_unstemmed | C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma |
| title_short | C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma |
| title_sort | c reactive protein is an indicator of the immunosuppressive microenvironment fostered by myeloid cells in hepatocellular carcinoma |
| topic | CRP HCC immune microenviroment tumor associated macrophage tumor associated neutrophil |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.774823/full |
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