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.