TY - JOUR
T1 - The potential application of pd-1 blockade therapy for early-stage biliary tract cancer
AU - Umemoto, Kumiko
AU - Togashi, Yosuke
AU - Arai, Yasuhito
AU - Nakamura, Hiromi
AU - Takahashi, Shinichiro
AU - Tanegashima, Tokiyoshi
AU - Kato, Mikiya
AU - Nishikawa, Tsubasa
AU - Sugiyama, Daisuke
AU - Kojima, Motohiro
AU - Gotohda, Naoto
AU - Kuwata, Takeshi
AU - Ikeda, Masafumi
AU - Shibata, Tatsuhiro
AU - Nishikawa, Hiroyoshi
N1 - Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Biliary tract cancer (BTC) is an aggressive cancer with a poor prognosis partially due to the limited success in developing novel therapies, including molecularly targeted therapies and immunotherapies. Programmed cell death-1 (PD-1) blockade therapy is less effective against BTCs, necessitating further studies to understand the detailed immunological status of the tumor microenvironment (TME) in BTC. Here, we examined the immunological status of the TME in 37 BTCs with early-to late-stage disease, especially focusing on PD-1+CD8+ T cells. PD-1+CD8+ T cells, which are reportedly associated with the clinical response to PD-1 blockade therapy, were frequently observed in early-stage BTC and decreased with disease progression. Imaging mass cytometry for representative PD-1+CD8+TIL-high and-low patients demonstrated that tumor-infiltrating PD-1+CD8+ T cells were localized adjacent to tumor cells, whereas PD-1-CD8+ T cells were detected mainly in the stroma of the TME. In a mouse model, PD-1 expression by tumor-infiltrating CD8+ T cells was higher in smaller tumors and decreased with tumor growth. Consequently, large tumors became resistant to PD-1 blockade, while small tumors containing higher numbers of PD-1+CD8+ T cells were sensitive. We propose the important role of tumor-infiltrating PD-1+CD8+ T cells in anti-tumor immunity and the potential application of PD-1 blockade therapy for early-stage BTC.
AB - Biliary tract cancer (BTC) is an aggressive cancer with a poor prognosis partially due to the limited success in developing novel therapies, including molecularly targeted therapies and immunotherapies. Programmed cell death-1 (PD-1) blockade therapy is less effective against BTCs, necessitating further studies to understand the detailed immunological status of the tumor microenvironment (TME) in BTC. Here, we examined the immunological status of the TME in 37 BTCs with early-to late-stage disease, especially focusing on PD-1+CD8+ T cells. PD-1+CD8+ T cells, which are reportedly associated with the clinical response to PD-1 blockade therapy, were frequently observed in early-stage BTC and decreased with disease progression. Imaging mass cytometry for representative PD-1+CD8+TIL-high and-low patients demonstrated that tumor-infiltrating PD-1+CD8+ T cells were localized adjacent to tumor cells, whereas PD-1-CD8+ T cells were detected mainly in the stroma of the TME. In a mouse model, PD-1 expression by tumor-infiltrating CD8+ T cells was higher in smaller tumors and decreased with tumor growth. Consequently, large tumors became resistant to PD-1 blockade, while small tumors containing higher numbers of PD-1+CD8+ T cells were sensitive. We propose the important role of tumor-infiltrating PD-1+CD8+ T cells in anti-tumor immunity and the potential application of PD-1 blockade therapy for early-stage BTC.
KW - Pd-1+cd8+ t cell
KW - Regulatory t cell
KW - Tumor microenvironment
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U2 - 10.1093/intimm/dxaa080
DO - 10.1093/intimm/dxaa080
M3 - Article
C2 - 31867666
AN - SCOPUS:85083622506
VL - 32
SP - 273
EP - 281
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 4
ER -