S quamous cell carcinoma antigen 1 is associated to poor prognosis in esophageal cancer through immune surveillance impairment and reduced chemosensitivity

Squamous cell carcinoma antigen‐1 ( SCCA 1) overexpression is associated with poor prognosis and chemoresistance in several tumor types, however, the underlying mechanisms remain elusive. Here, we report SCCA 1 in relation to the immune and peritumoral adipose tissue microenvironment in early and advanced esophageal adenocarcinoma ( EAC ). In our series of patients with EAC, free SCCA 1 serum levels were associated with significantly worse overall survival, and SCCA 1‐IgM serum levels showed a trend to a worse overall survival. Serum SCCA 1 and intratumoral SCCA 1 were inversely correlated with immune activation markers. In agreement with these findings, SCCA 1 induced the expression of the immune checkpoint molecule programmed death ligand‐1 on monocytes and a direct correlation of these 2 molecules was observed in sequential tumor sections. Furthermore, SCCA 1 mRNA expression within the tumor was inversely correlated with stem cell marker expression both within the tumor and in the peritumoral adipose tissue. In vitro, in EAC cell lines treated with different chemotherapeutic drugs, cell viability was significantly modified by SCCA 1 presence, as cells overexpressing SCCA 1 were significantly more resistant to cell death. In conclusion, poor prognosis in EAC overexpressing SCCA 1 is due to reduced tumor chemosensitivity as well as intratumoral immunity impairment, likely induced by this molecule .