Programmed death ligand 1 (PD-L1) expression and tumor microenvironment: Implications for patients with oral precancerous lesions

被引:69
作者
Yagyuu, Takahiro [1 ]
Hatakeyama, Kinta [2 ]
Imada, Mitsuhiko [1 ]
Kurihara, Miyako [1 ]
Matsusue, Yumiko [1 ]
Yamamoto, Kazuhiko [1 ]
Obayashi, Chiho [2 ]
Kirita, Tadaaki [1 ]
机构
[1] Nara Med Univ, Dept Oral & Maxillofacial Surg, 840 Shijo Cho, Kashihara, Nara 6348521, Japan
[2] Nara Med Univ, Dept Diagnost Pathol, 840 Shijo Cho, Kashihara, Nara 6348521, Japan
关键词
Oral cancer; Oral leukoplakia; Programmed cell death 1-ligand 1; CD163; Macrophage; Tumor-infiltrating lymphocyte; SQUAMOUS-CELL CARCINOMA; PREMALIGNANT LESIONS; INFILTRATING LYMPHOCYTES; MALIGNANT-TRANSFORMATION; EPITHELIAL DYSPLASIA; LICHEN-PLANUS; T-CELLS; CANCER; MACROPHAGES; LEUKOPLAKIA;
D O I
10.1016/j.oraloncology.2017.03.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives: Cancer immunoediting represents a relatively novel concept attempting to explain the process of tumor escape from the host immune system response. Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1), the tumor microenvironment, and tumor escape mechanisms that allow malignant transformation of oral precancerous lesions. Materials and methods: Patients with oral precancerous lesions managed at the Nara Medical University Hospital, Japan, (n = 120) were enrolled in this study. Epithelial dysplasias were graded by experienced pathologists, and subepithelial PD-L1-, CD163-, and CD8-positive cells were counted in the superficial lamina propria of oral mucosa. Epithelial PD-L1 expression was evaluated according to the staining intensity. The association of clinicopathological factors with epithelial dysplasia, malignant-free survival time, and significance of risk factors for malignant transformation were determined. Results: Multivariate analysis showed that the subepithelial CD163-positive cell count was the only significant risk factor for high-grade epithelial dysplasia (P < 0.001), while subepithelial CD163- and PD-L1-positive cell counts, and epithelial PD-L1 positivity were significantly associated with malignant-free survival (P = 0.004, 0.04, and < 0.001, respectively). Subepithelial PD-L1-positive cell count and epithelial PD-L1 positivity were significantly associated with malignant transformation (P = 0.01 and 0.04, respectively). Conclusion: Our results indicate that PD-L1-expressing dysplastic epithelial and recruited subepithelial cells in oral precancerous legions may evade the host immune system, and that the inhibition of PD-1/PD-L1 pathway may potentially prevent malignant transformation of oral precancerous legions as well as can treat advanced cancers. (C) 2017 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:36 / 43
页数:8
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