High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments

Abstract

The markers of the tumor microenvironment (TME) are promising prognostic and predictive factors in oral squamous cell carcinoma (OSCC). The current study aims to analyze the immunohistochemical expression of programmed cell death-ligand 1 (PD-L1) and interleukin-33 (IL-33) in a cohort of 95 chemonaïve OSCCs. PD-L1 and IL-33 were assessed separately in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). High PD-L1 expression in TILs was associated with better overall survival (OS) in univariate analysis. Tumors localized in the floor of the oral cavity and tongue tended to have a lower percentage of PD-L1-positive TCs when compared to other locations. PD-L1 expression on TCs had no prognostic significance when the whole cohort was analyzed. However, along with the T descriptor (TNM 8^th), it was included in the multivariable model predicting death in carcinomas of the floor of the oral cavity and tongue (HR = 2.51, 95% CI = 1.97-5.28). In other locations, only nodal status was identified as an independent prognostic factor in multivariate analysis (HR = 0.24, 95% CI = 0.08-0.70). Expression of IL-33 had no impact on survival, but it was differently expressed in various locations. In conclusion, the prognostic significance of PD-L1 in oral cancer depends on the tumor site and type of cell expressing immune checkpoint receptor (TCs vs. TILs).

Keywords: IL-33; PD-L1; immunohistochemistry; interleukin 33; oral squamous cell carcinoma; prognosis; programmed cell death-ligand 1.

Figure 1

Representative examples of PD-L1 staining (magnification ×10). (A) A few tumor cells with weak expression of PD-L1; (B) Intense expression of PD-L1 in the majority tumor cells and weak staining in TILs at the tumor–stroma interface; (C) Very weak expression of PD-L1 on single lymphocytes and negative on cancer cells; (D) High expression of PD-L1 on TILs at the tumor–stroma interface and negative on tumor cells.

Figure 2

Representative examples of IL-33 staining (magnification ×10). (A) Tumor cells lacking IL-33 expression (no staining); (B) Positive nuclear staining with heterogeneous intensity in tumor cells; (C) TILs with negative IL-33 staining; (D) Weak positive nuclear staining in TILs and negative in TCs.

Figure 3

Kaplan–Meier curves for overall survival according to PD-L1 expression on TCs (A), and TILs (B). PD-L1 expression on TCs had no impact on the outcomes in the whole cohort. High PD-L1 expression on TILs was associated with superior overall survival. p values were calculated with the log-rank test. Abbreviations: TC—tumor cells; TILs—tumor-infiltrating lymphocytes.

Figure 4

Overall survival probability curve according to PD-L1 expression on TCs (A) and TILs (B) in OSCCs of the tongue/floor of the oral cavity (A,B). There was a trend towards worse overall survival in cancers of the tongue/floor of the oral cavity with high PD-L1 expression on TCs. An opposite trend was observed for PD-L1 expression on TILs. p values were calculated with the log-rank test. Abbreviations: TCs—tumor cells; TILs—tumor infiltrating lymphocytes; OSCC—oral squamous cell carcinoma.

Figure 5

Overall survival probability curve according to PD-L1 expression on TCs in T3–T4 tumors of the tongue/floor of the oral cavity. Tumors with high PD-L1 expression on TCs had dismal outcomes. p value was calculated with the log-rank test. Abbreviations: TCs—tumor cells.

Figure 6

Overall survival probability curves according to PD-L1 expression on TCs (A) and TILs (B) in other oral compartments. There was a trend toward better survival in tumors characterized by high PD-L1 expression on TCs. Tumors rich in PD-L1-positive TILs had superior outcomes. p values were calculated with the log-rank test. Abbreviations: TCs—tumor cells; TILs—tumor infiltrating lymphocytes.