Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
PurposeImmune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab (N/I) are important treatment options for advanced renal cell carcinoma (RCC). The tumor microenvironment (TME) in these ICI-treated patients is largely unknown.MethodsTwenty-four patients treated with N/I between July 2015...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.969569/full |
| _version_ | 1798001423657467904 |
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| author | Jwa Hoon Kim Jwa Hoon Kim Gi Hwan Kim Yeon-Mi Ryu Sang-Yeob Kim Hyung-Don Kim Shin Kyo Yoon Yong Mee Cho Jae Lyun Lee |
| author_facet | Jwa Hoon Kim Jwa Hoon Kim Gi Hwan Kim Yeon-Mi Ryu Sang-Yeob Kim Hyung-Don Kim Shin Kyo Yoon Yong Mee Cho Jae Lyun Lee |
| author_sort | Jwa Hoon Kim |
| collection | DOAJ |
| description | PurposeImmune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab (N/I) are important treatment options for advanced renal cell carcinoma (RCC). The tumor microenvironment (TME) in these ICI-treated patients is largely unknown.MethodsTwenty-four patients treated with N/I between July 2015 and June 2020 were analyzed. Multiplexed immunohistochemistry (mIHC) was conducted to define the TME, including various T cell subsets, B cells, macrophages, and dendritic cells.ResultsThe median age of the study patients was 61 years (range, 39–80) and 75.0% of these cases were men. The objective response rate with N/I was 50.0%. The densities of the CD8+ cytotoxic T cells (P=0.005), specifically CD137+ CD8+ T cells (P=0.017), Foxp3- CD4+ helper T cells (P=0.003), Foxp3+ CD4+ regulatory T cells (P=0.045), CD68+ CD206- M1 macrophages (P=0.008), and CD68+ CD206+ M2 macrophages (P=0.021) were significantly higher in the treatment responders. At a median follow-up duration of 24.7 months, the median progression-free survival (PFS) was 11.6 months. The high densities (≥median) of Foxp3- CD4+ helper T cells (P=0.016) and CD68+ CD206- M1 macrophages (P=0.008) were significantly associated with better PFS, and the density of CD137+ CD8+ cytotoxic T cells (P=0.079) was marginally associated with better PFS. After multivariate analysis, the higher density of Foxp3- CD4+ helper T cells was independently associated with better PFS (hazard ratio 0.19; P=0.016).ConclusionThe properties and clinical implications of the TME properties in RCC indicate that Foxp3- CD4+ helper T cells, M1 macrophages, and CD137+ CD8+ T cells are potential predictive biomarkers and treatment targets. |
| first_indexed | 2024-04-11T11:36:01Z |
| format | Article |
| id | doaj.art-b36f52f473fe4abda40a72339493b1a4 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T11:36:01Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-b36f52f473fe4abda40a72339493b1a42022-12-22T04:25:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.969569969569Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumabJwa Hoon Kim0Jwa Hoon Kim1Gi Hwan Kim2Yeon-Mi Ryu3Sang-Yeob Kim4Hyung-Don Kim5Shin Kyo Yoon6Yong Mee Cho7Jae Lyun Lee8Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDivision of Oncology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South KoreaDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDepartment of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South KoreaDepartment of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South KoreaDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaPurposeImmune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab (N/I) are important treatment options for advanced renal cell carcinoma (RCC). The tumor microenvironment (TME) in these ICI-treated patients is largely unknown.MethodsTwenty-four patients treated with N/I between July 2015 and June 2020 were analyzed. Multiplexed immunohistochemistry (mIHC) was conducted to define the TME, including various T cell subsets, B cells, macrophages, and dendritic cells.ResultsThe median age of the study patients was 61 years (range, 39–80) and 75.0% of these cases were men. The objective response rate with N/I was 50.0%. The densities of the CD8+ cytotoxic T cells (P=0.005), specifically CD137+ CD8+ T cells (P=0.017), Foxp3- CD4+ helper T cells (P=0.003), Foxp3+ CD4+ regulatory T cells (P=0.045), CD68+ CD206- M1 macrophages (P=0.008), and CD68+ CD206+ M2 macrophages (P=0.021) were significantly higher in the treatment responders. At a median follow-up duration of 24.7 months, the median progression-free survival (PFS) was 11.6 months. The high densities (≥median) of Foxp3- CD4+ helper T cells (P=0.016) and CD68+ CD206- M1 macrophages (P=0.008) were significantly associated with better PFS, and the density of CD137+ CD8+ cytotoxic T cells (P=0.079) was marginally associated with better PFS. After multivariate analysis, the higher density of Foxp3- CD4+ helper T cells was independently associated with better PFS (hazard ratio 0.19; P=0.016).ConclusionThe properties and clinical implications of the TME properties in RCC indicate that Foxp3- CD4+ helper T cells, M1 macrophages, and CD137+ CD8+ T cells are potential predictive biomarkers and treatment targets.https://www.frontiersin.org/articles/10.3389/fonc.2022.969569/fullrenal cell carcinomatumor microenvironmentimmune checkpoint inhibitorsresponsesurvival |
| spellingShingle | Jwa Hoon Kim Jwa Hoon Kim Gi Hwan Kim Yeon-Mi Ryu Sang-Yeob Kim Hyung-Don Kim Shin Kyo Yoon Yong Mee Cho Jae Lyun Lee Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab Frontiers in Oncology renal cell carcinoma tumor microenvironment immune checkpoint inhibitors response survival |
| title | Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab |
| title_full | Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab |
| title_fullStr | Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab |
| title_full_unstemmed | Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab |
| title_short | Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab |
| title_sort | clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab |
| topic | renal cell carcinoma tumor microenvironment immune checkpoint inhibitors response survival |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.969569/full |
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