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Expression of immunoregulatory molecules PD-L1 and PD-1 in oral cancer and precancerous lesions: A cohort study of Japanese patients
Authors:Atsumu Kouketsu  Ikuro Sato  Mariko Oikawa  Yoshinaka Shimizu  Hiroki Saito  Tetsu Takahashi  Hiroyuki Kumamoto
Affiliation:1. Division of Oral and Maxillofacial Surgery, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry (Head of the institution: Tetsu Takahashi), 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan;2. Department of Pathology, Miyagi Cancer Center (Head of the institution: Ikuro Sato), 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi 981-1293, Japan;3. Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry (Head of the institution: Hiroyuki Kumamoto), 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Abstract:

Objective

An association of the programmed cell death-1 (PD-1) and its ligand PD-L1 with various types of malignant tumors has been established. This study aimed to investigate the role of the PD-L1/PD-1 pathway in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL).

Materials and methods

We examined 106 OSCC and 79 OEPL specimens for PD-L1 and PD-1 expression by immunohistochemistry. The results were compared with clinicopathological features of OSCC patients.

Results

In OSCC and OEPL specimens, PD-L1 expression was detected predominantly in epithelial or carcinoma cells, whereas PD-1 expression was found mainly in infiltrating or stromal lymphocytes. Seventy-two OSCC (67.9%) and 21 OEPL (26.6%) specimens were positive for PD-L1, and 73 OSCC (68.9%) and 23 OEPL (29.2%) specimens were positive for PD-1. PD-L1 and PD-1 expression levels were significantly different between OEPL and OSCC specimens (P < 0.001). There were significant positive correlations between PD-L1 and PD-1 expression in OEPL and OSCC specimens (P < 0.001). PD-L1 and PD-1 immunoreactivity was significantly associated with tumor size (P < 0.05). PD-L1 and PD-1 immunoreactivity in cases with advanced TNM staging was significantly higher than that in low staging cases (P < 0.01). There were significant correlations between PD-L1 and PD-1 expression in OSCC specimens and pathological variables such as stromal lymphocytic reaction (P < 0.05) and invasion depth (P < 0.01).

Conclusion

PD-L1 and PD-1 immunohistochemical status may be related to carcinogenesis, tumor progression, and prognosis in oral epithelial lesions. Agents targeting PD-1 and PD-L1 might be useful for OSCC treatment.
Keywords:Programmed cell death ligand 1  Programmed cell death 1  Oral cancer  Squamous cell carcinoma  Oral epithelial precursor lesions
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