Elsevier

Oral Oncology

Volume 68, May 2017, Pages 36-43
Oral Oncology

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

https://doi.org/10.1016/j.oraloncology.2017.03.006Get rights and content
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Highlights

  • The majority of CD163+ and CD8+ cells are found in the superficial lamina propria.

  • Increase in CD163+ cell number represents a risk factor for high-grade dysplasia.

  • Subepithelial PD-L1+ cell number is associated with malignant transformation risk.

  • Epithelial PD-L1 positivity is associated with malignant transformation risk.

  • PD-L1 inhibition may prevent malignant transformation of oral precancerous legions.

Abstract

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.

Abbreviations

CIS
carcinoma in situ
H&E
hematoxylin and eosin
PD-1
programmed death 1
PD-L1
programmed death ligand 1
SIN
squamous intraepithelial neoplasia
TAM
tumor-associated macrophage
TIL
tumor-infiltrating lymphocyte

Keywords

Oral cancer
Oral leukoplakia
Programmed cell death 1-ligand 1
CD163
Macrophage
Tumor-infiltrating lymphocyte

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