Prognostic value of immune checkpoint molecules in head and neck cancer: a meta-analysis

Abstract

Immune checkpoint molecules are important targets in cancer immunotherapy, but their association with prognosis in patients with head and neck cancer is controversial. In this meta-analysis, we searched for 12 immune checkpoint molecules in the PubMed, Embase and Cochrane Library databases and retrieved 52 studies with 7127 participants. Among the molecules included in the search, indoleamine 2, 3-dioxygenase (IDO), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) met the inclusion criteria for further analysis. Higher expression of IDO was associated with poorer overall survival in head and neck cancer patients (P = 0.011), but higher expression of PD-L1 correlated with better overall survival specifically in nasopharyngeal carcinoma patients (P = 0.01). In a sensitivity analysis, higher PD-L1 expression correlated with better progression-free survival (P = 0.043), and was associated with better overall survival in Caucasian subjects (P = 0.02), nasopharyngeal carcinoma patients (P = 0.015), and studies with small sample sizes (P = 0.001). PD-1 had no prognostic significance. There was no publication bias affecting the results. Thus, among the immune checkpoint molecules, IDO and PD-L1 are potential prognostic predictors in head and neck cancer.

Keywords: head and neck cancer; immune checkpoint molecule; meta-analysis; prognosis; survival.

Figure 1. Flow diagram of studies identified, included and excluded.

Figure 2. Overall forest plot of stratified analysis based on the type of molecule for the association of immune checkpoint molecules with OS.

Figure 3. Overall forest plot of stratified analysis based on the tumor location for the association between PD-L1 and OS.

Figure 4

Overall forest plots of sensitivity analysis. (A) Stratified analysis based on the tumor location for the association between PD-L1 and OS. (B) Overall forest plots of sensitivity analysis for the association between PD-L1 and PFS.

Figure 5

Begg’s funnel plots of publication bias on the relationships between immune checkpoint molecules and OS in all studies (A), PD-L1-associated studies (B) and high-quality studies on PD-L1 (C).