Programmed death-ligand 1 expression is associated with local invasion and distant metastases in differentiated thyroid cancer: Systematic review and meta-analysis

Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that tumors exploit to evade T-cell-mediated surveillance. While PD-L1 overexpression has been linked to advanced disease and poor prognosis in many cancers, its clinicopathological significance in differentiated thyroid cancer (DTC) remains unclear. We conducted a systematic review and meta-analysis by searching MEDLINE, Embase, the Cochrane Library, and PubMed from inception to 2 January, 2023. Eligible studies reported PD-L1 immunohistochemical positivity in DTC and its correlation with clinicopathological features. Data were extracted in duplicate, and study quality was assessed with a modified Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was evaluated by the I² value. Twelve retrospective studies met the inclusion criteria. All were retrospective and of moderate quality. High tumoral PD-L1 expression was significantly associated with the presence of lymphovascular invasion (LVI) (pooled OR 4.2, 95% CI 1.7-10.5), extrathyroidal extension (ETE) (pooled OR 1.7, 95% CI 1.2-2.4; <i>p</i> = 0.005) and distant metastases (pooled OR 4.6, 95% CI 1.6-13.0; <i>p</i> = 0.004). In other words, PD-L1-positive tumors were more likely to exhibit local invasion and distant metastasis. By contrast, PD-L1 status showed no significant association with tumor size, multifocality, lymph node metastasis, AJCC tumor stage, disease recurrence, or disease-specific mortality (<i>p</i> > 0.05 for all). Between-study heterogeneity was not significant for our key outcomes. PD-L1 overexpression in DTC is associated with a higher risk of local invasion and distant metastases, suggesting that PD-L1 may contribute to tumor progression via immune evasion.