Lectin-like Transcript-1 (LLT1) Expression in Oral Squamous Cell Carcinomas: Prognostic Significance and Relationship with the Tumor Immune Microenvironment

Abstract

Lectin-like transcript-1 (LLT1) expression is detected in different cancer types and is involved in immune evasion. The present study investigates the clinical relevance of tumoral and stromal LLT1 expression in oral squamous cell carcinoma (OSCC), and relationships with the immune infiltrate into the tumor immune microenvironment (TIME). Immunohistochemical analysis of LLT1 expression was performed in 124 OSCC specimens, together with PD-L1 expression and the infiltration of CD20⁺, CD4⁺, and CD8⁺ lymphocytes and CD68⁺ and CD163⁺-macrophages. Associations with clinicopathological variables, prognosis, and immune cell densities were further assessed. A total of 41 (33%) OSCC samples showed positive LLT1 staining in tumor cells and 55 (44%) positive LLT1 in tumor-infiltrating lymphocytes (TILs). Patients harboring tumor-intrinsic LLT1 expression exhibited poorer survival, suggesting an immunosuppressive role. Conversely, positive LLT1 expression in TILs was significantly associated with better disease-specific survival, and also an immune-active tumor microenvironment highly infiltrated by CD8⁺ T cells and M1/M2 macrophages. Furthermore, the combination of tumoral and stromal LLT1 was found to distinguish three prognostic categories (favorable, intermediate, and adverse; p = 0.029, Log-rank test). Together, these data demonstrate the prognostic relevance of tumoral and stromal LLT1 expression in OSCC, and its potential application to improve prognosis prediction and patient stratification.

Keywords: PD-L1; TILs; oral squamous cell carcinomaLLT1; prognosis.

Figure 1

Immunohistochemical analysis of LLT1 in OSCC tissue specimens. Representative images of tumors showing (A) negative LLT1 expression (score = 0); two examples of tumoral LLT1 expression showing (B) weak (score = 1) and (C) moderate staining (score = 2); three examples of stromal LLT1 expression showing (D) mild to moderate positive TILs (score = 1); (E) abundant (score = 2); and (F) highly abundant positive TILs (score = 3). Scale bar, 200 µm. Magnification, 20×.

Figure 2

Kaplan–Meier disease-specific survival in the cohort of 125 OSCC patients categorized by (A) tumoral LLT1 expression (positive versus negative), (B) stromal LLT1 expression in TILs (positive versus negative), and (C) combination of tumoral and stromal LLT1 expression into either four or (D) three prognostic subgroups (favorable, intermediate, and adverse). p-values were estimated with the Log-rank test.