Abstract
BACKGROUND: The tumor microenvironment (TME) exerts a profound influence on the progression of cancer cells. Tumor-associated macrophages (TAMs), the most abundant cell population within the TME, exhibit a complex, dual role. On the one hand, TAMs promote inflammation and help eliminate cancer cells; on the other hand, they often adopt an anti-inflammatory role that contributes to the evolution of cancer cells. Furthermore, the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway plays a critical role in both the adaptive and innate immune responses. This study aims to understand the roles of TAMs and the PD-1/PD-L1 signaling network in esophageal cancer. METHODS: We conducted a systematic review of published data using the Medline (PubMed), Scopus, and Cochrane databases. We included articles that investigated the coexistence of TAMs and the PD-1/PD-L1 pathway in esophageal cancer. Studies that evaluated the clinical prognosis of patients with elevated levels of PD-1-positive TAMs were also incorporated. RESULTS: Six articles comprising a total of 822 patients were included in the review. The data indicate a positive correlation between PD-L1 expression and TAMs infiltration. Additionally, patients with high levels of PD-1-positive TAMs tend to have a worse prognosis compared with those with lower levels. CONCLUSIONS: TAMs play a crucial role in regulating the PD-1/PD-L1 network and the progression of esophageal cancer. Further studies are necessary, however, to clarify the roles of TAMs and the PD-1/PD-L1 network in esophageal cancers.