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KMID : 0939920210530010162
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대한암학회지
2021 Volume.53 No. 1 p.162 ~ p.171
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Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer
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Kim Hyung-Don
Kim Jwa-Hoon
Ryu Yeon-Mi
Kim Dan-Bee
Lee Sun-Min
Shin Jae-Hoon
Hong Seung-Mo
Kim Ki-Hun
Jung Dong-Hwan
Song Gi-Won
Hwang Dae-Wook
Lee Jae-Hoon
Song Ki-Byung
Ryoo Baek-Yeol
Jeong Jae-Ho
Kim Kyu-Pyo
Kim Sang-Yeob
Yoo Chang-Hoon
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Abstract
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Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results: The density of CD8+ T cells, FoxP3? CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3? CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3? CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3? CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion: The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3? CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.
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KEYWORD
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Biliary tract neoplasms, Multiplexed immunohistochemistry, Tumor margin, CD4+ helper T cells
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