Publications

The potential application of PD1 blockade therapy for early stage biliary tract cancer

Umemoto, K., Togashi, Y., Arai, Y., et al.

Biliary tract cancer (BTC) is an aggressive cancer with a poor prognosis partially due to the limited success in developing novel therapies, including molecular-targeted therapies and immunotherapies. 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 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, was 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 antitumor immunity and the potential application of PD-1 blockade therapy for early-stage BTC.

Citation

Umemoto, K., Togashi, Y., Arai, Y., et al. "The potential application of PD1 blockade therapy for early stage biliary tract cancer" International Immunology (2019): doi: 10.1093/intimm/dxz080