Overexpression of immunomodulatory mediators in oral precancerous lesions

Area of Science:

• Immunology
• Oncology
• Oral Pathology

Background:

• Immune evasion is crucial for tumor development.
• Proteins such as Human Leukocyte Antigen (HLA) G and E, Programmed Cell Death 1 Ligand 1 (PD-L1), Interleukin-10 (IL-10), and Transforming Growth Factor-beta (TGF-β) are implicated in suppressing antitumor immune responses.
• Understanding these mediators in oral precancer is vital for predicting malignant transformation.

Purpose of the Study:

• To investigate the expression of key immunomodulatory proteins (HLA-G, HLA-E, PD-L1, IL-10, TGF-β2, TGF-β3) in oral leukoplakia (OL).
• To determine if the expression of these molecules correlates with the risk of malignant transformation in OL.
• To compare the expression levels in OL with normal oral mucosa and oral squamous cell carcinoma (OSCC).

Main Methods:

• Tissue samples from OL (n=80), normal mucosa (n=20), and OSCC (n=20) were analyzed.
• Immunohistochemistry was used to assess protein expression in tissues.
• Enzyme-Linked Immunosorbent Assay (ELISA) was employed to measure salivary concentrations of specific proteins (sHLA-G, IL-10, TGF-β).

Main Results:

• Expression of HLA-G, HLA-E, PD-L1, IL-10, TGF-β2, and TGF-β3 was significantly higher in OL compared to normal mucosa (P<0.05) and comparable to OSCC (P>0.05).
• The number of granzyme B+ cells was lower in OL compared to OSCC (P<0.01) but similar to controls (P=0.28).
• Salivary levels of sHLA-G, IL-10, and TGF-β did not differentiate between OL and healthy individuals.

Conclusions:

• Overexpression of immunosuppressive mediators in OL indicates a significant potential for immune evasion.
• This immune evasion appears independent of the degree of epithelial dysplasia and the proliferation/apoptosis status within the lesion.
• The findings highlight the role of these proteins in the immune microenvironment of oral precancer, potentially influencing malignant progression.