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 .