Correlation of PD-1 and PD-L1 expression in oral leukoplakia and oral squamous cell carcinoma: an immunohistochemical study

Abstract

The programmed cell death protein (PD-1)/programmed cell death protein ligand (PD-L1) pathway and cytotoxic T lymphocyte antigen are the most important co-stimulatory molecules that play a key role in the negative regulation of T cells during carcinogenesis. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in oral leukoplakia and squamous cell carcinoma compared with normal oral mucosa. Twenty-five cases of oral squamous cell carcinoma, oral leukoplakia and normal oral mucosa tissue specimens were immunohistochemically stained to assess PD-1 and PD-L1 expression. The PD-L1 positivity of subepithelial TAFs (p < 0.001) increased with increasing grades of oral leukoplakia. Pearson's correlation indicated a high positive correlation between the PD-L1 labelling index of epithelial tumour cells and the PD-1 labelling index of tumour infiltrating lymphocytes (p value: 0.005) in OSCC. A high positive correlation was noted between the H-score of PD-L1 positive tumour epithelial cells and the H-score of PD-1 positive tumour infiltrating lymphocytes in OSCC (p value: 0.001). PD-L1 positivity increased in dysplastic epithelial cells from premalignant lesions to malignancy. The sub-epithelial PD-L1 positive TAFs were higher in oral leukoplakia compared to OSCC inferring that PD-L1 positivity in TAFs decreased with malignant transformation. The PD-1 positivity in TILs was higher in oral leukoplakia than in OSCC.

Figure 1

Photo micrograph showing immunohistochemical expression. (a) Tonsillar epithelium as positive control of PD-L1 (400×) (black arrow heads). (b) Tonsillar lymphocytesas positive control for PD-1 (400×) (black arrow heads).

Figure 2

Photo micrograph showing immunohistochemical expression. (a) Membranous expression of PD-L1 in epithelial tumour cells present in the invasive front of oral squamous cell carcinoma (400×) (black arrow heads). (b) Membranous expression of PD-L1 in tumour associated fibroblast cells present in the invasive front of oral squamous cell carcinoma (400×) (black arrow heads). (c) Membranous expression of PD-1 in tumour- infiltrating lymphocytes (TILs) present in the invasive front of oral squamous cell carcinoma (400×) (black arrow heads). (d) Membranous expression of PD-L1 in dysplastic basal epithelial cells of oral leukoplakia (400×) (black arrow heads). (e) Membranous expression of PD-L1 in tumour associated fibroblast cells present subepithelial stroma of oral leukoplakia (400×) (black arrow heads). (f) Membranous expression of PD-1 infiltrating lymphocytes present in subepithelial stroma of oral leukoplakia (400×) (black arrow heads).

Figure 3

(a) Photo micrograph showing immunonegativity for PD-L1 in Normal Oral Mucosa. (b) Photo micrograph showing immunonegativity for PD-1 in Normal Oral Mucosa.