Squamous Cell Carcinoma Antigen (SCCA1) overexpression is associated to poor prognosis and chemoresistance in several tumor types, however, the underlying mechanisms remain still elusive. Here, we report SCCA1 relation to the immune and peritumoral adipose tissue microenvironment in early and advanced esophageal adenocarcinoma (EAC). In our series of esophageal adenocarcinoma patients, free SCCA1 serum levels were associated with a significant worse overall survival, while SCCA1-IgM serum levels showed a trend to a worse overall survival. Serum SCCA1 and intratumoral SCCA1 were inversely correlated with immune activation markers. In agreement with these findings, SCCA1 induced the expression of the immune checkpoint molecule PD-L1 on monocytes and a direct correlation of these two molecules was observed in sequential tumor sections. Furthermore, SCCA1 mRNA expression within the tumor was inversely correlated with stem cells markers 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 SCCA1 presence, since cells overexpressing SCCA1 were significantly more resistant to cell death. In conclusion, poor prognosis in EAC overexpressing SCCA1 is due to reduced tumor chemo sensitivity as well as an intratumoral immunity impairment, likely induced by this molecule. This article is protected by copyright. All rights reserved.

SCCA1 is associated to poor prognosis in esophageal cancer through immune surveillance impairment and reduced chemosensitivity

Turato, Cristian;Scarpa, Melania;Kotsafti, Andromachi;Cappon, Andrea;Quarta, Santina;Biasiolo, Alessandra;Cavallin, Francesco;Trevellin, Elisabetta;Guzzardo, Vincenza;Fassan, Matteo;Chiarion-Sileni, Vanna;Rugge, Massimo;Vettor, Roberto;Pontisso, Patrizia
2019

Abstract

Squamous Cell Carcinoma Antigen (SCCA1) overexpression is associated to poor prognosis and chemoresistance in several tumor types, however, the underlying mechanisms remain still elusive. Here, we report SCCA1 relation to the immune and peritumoral adipose tissue microenvironment in early and advanced esophageal adenocarcinoma (EAC). In our series of esophageal adenocarcinoma patients, free SCCA1 serum levels were associated with a significant worse overall survival, while SCCA1-IgM serum levels showed a trend to a worse overall survival. Serum SCCA1 and intratumoral SCCA1 were inversely correlated with immune activation markers. In agreement with these findings, SCCA1 induced the expression of the immune checkpoint molecule PD-L1 on monocytes and a direct correlation of these two molecules was observed in sequential tumor sections. Furthermore, SCCA1 mRNA expression within the tumor was inversely correlated with stem cells markers 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 SCCA1 presence, since cells overexpressing SCCA1 were significantly more resistant to cell death. In conclusion, poor prognosis in EAC overexpressing SCCA1 is due to reduced tumor chemo sensitivity as well as an intratumoral immunity impairment, likely induced by this molecule. This article is protected by copyright. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/3295494
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