Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
In: Front Oncol, 2022
academicJournal
Zugriff:
PURPOSE: Immune 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. METHODS: Twenty-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. RESULTS: The 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). CONCLUSION: The 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.
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Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
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Autor/in / Beteiligte Person: | Kim, Jwa Hoon ; Kim, Gi Hwan ; Ryu, Yeon-Mi ; Kim, Sang-Yeob ; Kim, Hyung-Don ; Yoon, Shin Kyo ; Cho, Yong Mee ; Lee, Jae Lyun |
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Zeitschrift: | Front Oncol, 2022 |
Veröffentlichung: | Frontiers Media S.A., 2022 |
Medientyp: | academicJournal |
DOI: | 10.3389/fonc.2022.969569 |
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