The potential application of PD-1 blockade therapy for early-stage biliary tract cancer.
The potential application of PD-1 blockade therapy for early-stage biliary tract cancer.
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DOI：
10.1093/intimm/dxz080
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发表时间：
2019-12
影响因子：
4.4
通讯作者：
K. Umemoto;Y. Togashi;Y. Arai;Hiromi Nakamura;Shinichirou Takahashi;T. Tanegashima;Mikiya Kato;T. Nishikawa;D. Sugiyama;M. Kojima;N. Gotohda;T. Kuwata;M. Ikeda;T. Shibata;H. Nishikawa
中科院分区：
文献类型：
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作者：
K. Umemoto;Y. Togashi;Y. Arai;Hiromi Nakamura;Shinichirou Takahashi;T. Tanegashima;Mikiya Kato;T. Nishikawa;D. Sugiyama;M. Kojima;N. Gotohda;T. Kuwata;M. Ikeda;T. Shibata;H. Nishikawa
胆道癌（BTC）是一种侵袭性癌症，预后不良，部分原因是开发新疗法（包括分子靶向疗法和免疫疗法）的成功有限。PD-1阻断疗法对BTC的有效性较低，需要进一步研究以了解BTC中肿瘤微环境（TME）的详细免疫状态。在这里，我们检查了37例具有早期至晚期疾病的BTC中TME的免疫状态，特别关注PD-1+ CD 8 + T细胞。据报道，PD-1+ CD 8 + T细胞与PD-1阻断治疗的临床应答相关，在早期BTC中经常观察到，并随着疾病进展而减少。代表性PD-1+ CD 8 + TIL-高和-低患者的成像质谱细胞术表明，肿瘤浸润的PD-1+ CD 8 + T细胞位于肿瘤细胞附近，而PD-1-CD 8 + T细胞主要在TME的基质中检测到。在小鼠模型中，肿瘤浸润性CD 8 + T细胞的PD-1表达在较小的肿瘤中较高，并随着肿瘤生长而降低。因此，大肿瘤变得对PD-1阻断具有抗性，而含有较高数量的PD-1+ CD 8 + T细胞的小肿瘤是敏感的。我们提出肿瘤浸润PD-1+ CD 8 + T细胞在抗肿瘤免疫中的重要作用以及PD-1阻断治疗早期BTC的潜在应用。
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.