Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma
Abstract Background Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectur...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04336-8 |
| _version_ | 1797773949350707200 |
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| author | Dawei Zhang Yuanli Ni Yongquan Wang Juan Feng Na Zhuang Jiatao Li Limei Liu Wenhao Shen Ji Zheng Wei Zheng Cheng Qian Juanjuan Shan Zhansong Zhou |
| author_facet | Dawei Zhang Yuanli Ni Yongquan Wang Juan Feng Na Zhuang Jiatao Li Limei Liu Wenhao Shen Ji Zheng Wei Zheng Cheng Qian Juanjuan Shan Zhansong Zhou |
| author_sort | Dawei Zhang |
| collection | DOAJ |
| description | Abstract Background Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. Methods Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. Results We found that ccRCC tissues had higher levels of CD8+ T cells, CD163− macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell–cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. Conclusion Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research. |
| first_indexed | 2024-03-12T22:13:41Z |
| format | Article |
| id | doaj.art-5383e55f90bf47299989a0dbd37113fb |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-12T22:13:41Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-5383e55f90bf47299989a0dbd37113fb2023-07-23T11:25:19ZengBMCJournal of Translational Medicine1479-58762023-07-0121111810.1186/s12967-023-04336-8Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinomaDawei Zhang0Yuanli Ni1Yongquan Wang2Juan Feng3Na Zhuang4Jiatao Li5Limei Liu6Wenhao Shen7Ji Zheng8Wei Zheng9Cheng Qian10Juanjuan Shan11Zhansong Zhou12Department of Urology, The Southwest Hospital, Army Medical UniversityChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalDepartment of Urology, The Southwest Hospital, Army Medical UniversityChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalDepartment of Urology, The Southwest Hospital, Army Medical UniversityDepartment of Urology, The Southwest Hospital, Army Medical UniversityAnesthesiology Department, The 80th Army Hospital of Chinese PLAChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalDepartment of Urology, The Southwest Hospital, Army Medical UniversityAbstract Background Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. Methods Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. Results We found that ccRCC tissues had higher levels of CD8+ T cells, CD163− macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell–cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. Conclusion Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.https://doi.org/10.1186/s12967-023-04336-8Clear cell renal cell carcinomaTumor microenvironmentImmune architectureCellular neighborhoodSurvival |
| spellingShingle | Dawei Zhang Yuanli Ni Yongquan Wang Juan Feng Na Zhuang Jiatao Li Limei Liu Wenhao Shen Ji Zheng Wei Zheng Cheng Qian Juanjuan Shan Zhansong Zhou Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma Journal of Translational Medicine Clear cell renal cell carcinoma Tumor microenvironment Immune architecture Cellular neighborhood Survival |
| title | Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma |
| title_full | Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma |
| title_fullStr | Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma |
| title_full_unstemmed | Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma |
| title_short | Spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma |
| title_sort | spatial heterogeneity of tumor microenvironment influences the prognosis of clear cell renal cell carcinoma |
| topic | Clear cell renal cell carcinoma Tumor microenvironment Immune architecture Cellular neighborhood Survival |
| url | https://doi.org/10.1186/s12967-023-04336-8 |
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