MZB1 in borderline resectable pancreatic cancer resected after neoadjuvant chemoradiotherapy

Background: A high accumulation of CD8(+) tumor- infiltrating lymphocytes (TILs) induced by neoadjuvant chemoradiotherapy (NACRT) is associated with a favorable prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the correlation between a high accumulation of CD8(+) TILs and a favorable prognosis has yet to be fully clarified. The aim of this study was to determine predictive markers of a high accumulation of CD8(+) TILs, with a favorable prognosis, using proteomic analysis. Materials and methods: We studied 72 resected borderline resectable PDAC patients treated with NACRT between April 2009 and March 2014. Three matched pairs of high CD8(+) TIL patients with a favorable prognosis and low CD8(+) TIL patients with a poor prognosis were selected. Shotgun proteomics of the stroma and cancerous lesion was performed using formalin- fixed, paraffin- embedded tissue. Validation of the identified proteins was performed using immunohistochemical staining. Relationships between the identified proteins and TILs and clinical outcomes were assessed. Results: Marginal zone B- and B1- cell- specific protein (MZB1) was detected in the tumor stroma. MZB1 expression was positively correlated with a high accumulation of CD8_ TILs. High stromal MZB1 expression also correlated with disease- free and overall survival. In a subgroup analysis of CD8(+) expression, there was a significant association between stromal MZB1 expression and disease- free and overall survival in the high CD8(+) TIL group. Conclusions: MZB1 is a potential marker of a high accumulation of CD8(+) TILs in borderline resectable PDACs resected after NACRT. Combination of CD8(+) TILs with MZB1 may be a new biomarker of resected cases after NACRT. (C) 2017 Elsevier Inc. All rights reserved.