Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases
Abstract Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expr...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03667-2 |
| _version_ | 1811194988514508800 |
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| author | Yangsong He Yanan Han A-hui Fan Danxiu Li Boda Wang Kun Ji Xin Wang Xiaodi Zhao Yuanyuan Lu |
| author_facet | Yangsong He Yanan Han A-hui Fan Danxiu Li Boda Wang Kun Ji Xin Wang Xiaodi Zhao Yuanyuan Lu |
| author_sort | Yangsong He |
| collection | DOAJ |
| description | Abstract Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Methods Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. Results The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68−CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. Conclusions The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68−CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects. |
| first_indexed | 2024-04-12T00:35:24Z |
| format | Article |
| id | doaj.art-8ed76419e5ec4330855c5f6962cd2575 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T00:35:24Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-8ed76419e5ec4330855c5f6962cd25752022-12-22T03:55:10ZengBMCJournal of Translational Medicine1479-58762022-10-0120111310.1186/s12967-022-03667-2Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastasesYangsong He0Yanan Han1A-hui Fan2Danxiu Li3Boda Wang4Kun Ji5Xin Wang6Xiaodi Zhao7Yuanyuan Lu8Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityDepartment of Gastroenterology, Tangdu Hospital, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityDepartment of Gastroenterology, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Gastroenterology, Tangdu Hospital, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityAbstract Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Methods Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. Results The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68−CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. Conclusions The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68−CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.https://doi.org/10.1186/s12967-022-03667-2Colorectal cancerLiver metastasisImmune microenvironmentImmunosuppressionComparison |
| spellingShingle | Yangsong He Yanan Han A-hui Fan Danxiu Li Boda Wang Kun Ji Xin Wang Xiaodi Zhao Yuanyuan Lu Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases Journal of Translational Medicine Colorectal cancer Liver metastasis Immune microenvironment Immunosuppression Comparison |
| title | Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases |
| title_full | Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases |
| title_fullStr | Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases |
| title_full_unstemmed | Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases |
| title_short | Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases |
| title_sort | multi perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases |
| topic | Colorectal cancer Liver metastasis Immune microenvironment Immunosuppression Comparison |
| url | https://doi.org/10.1186/s12967-022-03667-2 |
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