PD‐L1andHLA‐class I expression status and their therapeutic implication in oesophageal small‐cell carcinoma

Abstract

AimsOesophageal small‐cell carcinoma is a rare and highly aggressive subtype of oesophageal cancer with a dismal prognosis. To explore the potential applicability of immunotherapy, we investigated the expression status of programmed death ligand 1 (PD‐L1) and human leukocyte antigen (HLA)‐class I and the degree of tumour‐infiltrating lymphocytes (TILs) in oesophageal small‐cell carcinoma.Methods and resultsPD‐L1 and HLA‐class I expression levels were evaluated in 10 pure small‐cell carcinomas and five mixed neuroendocrine‐non‐neuroendocrine neoplasms (MiNENs). The combined positive score (CPS) and tumour proportion score (TPS) were used for PD‐L1 assessment. Immunohistochemistry for mismatch repair (MMR) proteins was also performed. PD‐L1 immunohistochemistry demonstrated CPS ≥1 in nine (60%), CPS ≥10 in five (33%), and TPS ≥1 in five (33%) cases. Overall survival was significantly longer in patients with CPS ≥1 than in those with CPS <1. HLA‐class I deficiency (>50% tumour cells) was noted in five cases (33%), with no significant correlation with PD‐L1 expression status. Among the five MiNENs, HLA‐class I expression was decreased in the small‐cell carcinoma component of three cases. HLA‐class I deficiency was significantly associated with higher TNM stage and reduced TIL levels. MMR deficiency was not observed in any case.ConclusionGiven that a significant subset (40%) exhibited PD‐L1 CPS ≥1 with preserved HLA‐class I expression and high levels of TIL, the PD‐1/PD‐L1 pathway is a potential therapeutic target for oesophageal small‐cell carcinoma.