Expression of PD‑L1 and CD4+ tumor‑infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma

Abstract

The clinical efficacy of immune checkpoint blockade has been recently demonstrated in a variety of cancer types. The aim of the present study was to characterize the expression profile of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) in head and neck squamous carcinoma (HNSCC). A total of 63 patients with HNSCC were enrolled in the present study. CD3 + and CD4 + TILs and the expression of PD-L1 were detected by immunohistochemistry. PD-L1 mRNA levels were evaluated by reverse transcription-quantitative PCR analysis. The association of TILs and PD-L1 with patient clinicopathological characteristics was also assessed. CD3 + and CD4 + TILs were detected in 100% of the samples. CD3 + was the predominant subset of TILs. PD-L1 was expressed in 53 of 61 (86%) patients when a score of ≥1 on tumor cells was considered positive and in 28 patients (45.2%) when a score of >5 on tumor cells was considered positive. PD-L1 mRNA levels were determined to be significantly correlated with PD-L1 protein expression. Survival analysis demonstrated that high CD4 + TILs were associated with improved overall survival (OS) and disease-free survival (DFS), and furthermore, the association of high PD-L1 expression with unfavorable OS and DFS was statistically significant. Multivariate analysis identified CD4 + TILs and PD-L1 as prognostic markers for HNSCC. The results of the present study suggested that increased CD4 + TILs in HNSCC may be associated with improved outcomes, while high expression of PD-L1 may indicate unfavorable OS and DFS; thus, these factors may serve as predictors of the response to immune checkpoint therapy.

Programmed Cell Death Ligand 1 Expression on Immune Cells and Survival in Patients With Nonmetastatic Head and Neck Cancer

“…A total of 3825 publications were identified, and of 82 eligible articles, 17 studies [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] met inclusion criteria and hence were considered eligible for our meta-analysis (Figure 1). Characteristics of these studies conducted in a total of 3190 patients with HNSCC at various sites (including the oral cavity,…”

“…A total of 3825 publications were identified, and of 82 eligible articles, 17 studies 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 met inclusion criteria and hence were considered eligible for our meta-analysis ( Figure 1 ). Characteristics of these studies conducted in a total of 3190 patients with HNSCC at various sites (including the oral cavity, oropharynx, larynx, and hypopharynx) with stage I through IV disease who underwent radical curative treatment are reported in Table 1 .…”

“…This systematic review and meta-analysis of 17 studies found that high PD-L1 expression levels on immune cells in the tumor immune microenvironment were associated with extended OS and specific survival in patients with localized and locoregionally advanced HNSCC. Further studies focused on this objective may be warranted to investigate whether high PD-L1 levels on immune cells may serve as a reliable and widely recognized prognostic marker.…”

“…While all studies exhibited low RoB using the Newcastle-Ottawa Quality Assessment Scale system (eTable 2 in Supplement 1), 7 studies 23,24,27,[30][31][32]35 showed moderate RoB that was associated with Results are presented from a random-effects model, including τ 2 (heterogeneity variance), I 2 (inconsistency index), H 2 (H statistics), and P value. aHR indicates adjusted hazard ratio; box size, weight of the aHR (effect size); dashed lines, overall pooled aHRs; diamonds, pooled aHRs; IC, immune cell; lateral points, 95% CIs; NA, not applicable; TC, tumor cell.…”

Immunotherapy for the Treatment of Squamous Cell Carcinoma: Potential Benefits and Challenges

“…Among the TILs, CD3, CD8 (effector/cytotoxic), and CD4 (helper) T cells are recognized to have an anti-tumor immune response and found to positively correlate with SCC patients’ favorable outcomes. One report showed that among 63 patients with HNSCC, all of the tumors have TILs positive for CD3 and CD4 immunohistochemistry, and increased CD4-positive cell infiltration was associated with improved survival compared with the poor CD4-positive cell-infiltrating tumors [ 111 ]. In another report, 50 patients with OSCC were assessed for CD8- and CD4-positive cells and they found that CD8-positive cells were more abundant than CD4 in tumor specimens and there is a negative correlation between CD8 infiltration and metastasis [ 112 ].…”