Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy

Abstract

The programmed death-1/programmed death-1 ligands (PD-1/PD-L) pathway plays an important role in immunological tumor evasion. However, the clinical significance of the PD-L (L1 and L2) expression in esophageal cancer treated with chemotherapy has not been fully investigated. We examined the expression of PD-L of the primary tumors obtained from 180 esophageal cancer patients who underwent radical resection with or without neoadjuvant chemotherapy (NAC) using immunohistochemical staining. The relationship between the expression patterns and clinico-pathological characteristics was examined. In the present study, 53 patients (29.4%) and 88 patients (48.3%) were classified into positive for PD-L1 and PD-L2 expression, respectively. In all the patients examined, overall survival rates of the patients with tumors positive for PD-L1 or PD-L2 were significantly worse than those with tumors negative for PD-L1 or PD-L2 (P = 0.0010 and P = 0.0237, respectively). However, subgroup analysis showed that these tendencies are only found in the patients treated with NAC, and not in those without NAC. The patients with positive PD-L1 expression had a significantly higher rate of NAC history (P = 0.0139), but those with positive PD-L2 expression did not have a significantly high rate of NAC history (P = 0.6127). There is no significant relationship between PD-L1 expression and response to chemotherapy (P = 0.3118), but patients with positive PD-L2 expression had significantly inferior responses to chemotherapy (P = 0.0034). The PD-1/PD-L pathway might be an immunological mechanism associated with the long-term effectiveness of chemotherapy in esophageal cancer patients. Further investigation into the roles of PD-1 pathway in chemotherapy could lead to the development of better treatment options for this disease.

Keywords: Chemotherapy; esophageal cancer; prognosis; programmed death-1-ligand; programmed death-2-ligand.