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Clinical Significance of PD-L1 Expression in Both Cancer and Stroma Cells of Cholangiocarcinoma Patients

Yuki Kitano MD, PhD, Yo-ichi Yamashita MD, PhD, FACS, Yosuke Nakao MD, Rumi Itoyama MD, Toshihiko Yusa MD, Naoki Umezaki MD, Masayo Tsukamoto MD, PhD, Takanobu Yamao MD, Tatsunori Miyata MD, PhD, Shigeki Nakagawa MD, PhD, Hirohisa Okabe MD, PhD, FACS, Katsunori Imai MD, PhD, FACS, Akira Chikamoto MD, PhD, FACS, Takatoshi Ishiko MD, PhD, FACS, Hideo Baba MD, PhD, FACS
Translational Research and Biomarkers
Online First ™ - August , 2019

Abstract

Background

The clinical significance of programmed death 1 and its ligand (PD-L1) as therapeutic targets has been reported previously. This study aimed to investigate the clinical impact of PD-L1 expression in cancer and stroma cells in cholangiocarcinoma (CCA).

Methods

The study enrolled 177 consecutive CCA patients who underwent curative resection between 2005 and 2014. Expression of PD-L1 in CCA and stroma cells was assayed by immunohistochemistry, and their relationships with patient clinicopathologic characteristics and prognoses were evaluated. Tumor-infiltrating immune cells (CD66b+ neutrophils [TANs] and CD163+ M2 macrophages [TAMs]) also were assayed by immunohistochemistry, and their relationship with PD-L1 expression in cancer and stroma cells was evaluated.

Results

Among the 177 analyzed CCA cases, PD-L1 expression was identified in cancer cells in 54 cases (30.5%) and in stroma cells in 77 cases (43.5%). The patients with positive PD-L1 expression in cancer and stroma cells had worse overall survival rates than those negative for PD-L1 (cancer cells: hazard ratio [HR] 2.08; P = 0.0004; stroma cells: HR 1.84; P = 0.003). Moreover, the patients with PD-L1-positive cancer cells had higher rates of PD-L1 expression in stroma cells (P < 0.0001) and higher numbers of TANs (P = 0.0003) and TAMs (P = 0.004) than those with low PD-L1 expression. In the multivariate analysis, PD-L1 expression in both cancer and stroma cells (HR 2.20; P = 0.002) was an independent predictor of poor overall survival.

Conclusions

The study showed PD-L1 expressed in both CCA and stromal cells and demonstrated that its expression may affect numbers of TANs and TAMs and play a pivotal role in CCA outcomes.

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