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

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.