Higher density of compact B cell clusters in invasive front may contribute to better prognosis in pancreatic ductal adenocarcinoma

侵袭前沿致密B细胞簇密度较高可能有助于胰腺导管腺癌的良好预后。

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Abstract

While the correlation between T cells and patient survival was widely investigated, the clinical significance of CD20(+) B cells in pancreatic ductal adenocarcinoma (PDAC) is less clear. We hypothesized that the spatial pattern of B cells within tumor microenvironment (TME) are more informative, which may reveal the prognostic significance for PDAC patients. Therefore, we developed a computer-based workflow to analyze CD20(+) B cells in whole slide images (WSI) from 45 cases of PDAC patients. Depending on this workflow, annotations of each case which were created by pathologists were subdivided for three regions, including invasive front (IF), cancer center (CT) and cancer island (CI) to explore the association between the spatial pattern of CD20(+) B cells and patient prognosis outcomes. After that, occupancy rate (as area under curve, occupancy AUC), fractal dimension differences (ΔFD), cluster density and coverage ratio were used to quantify the spatial pattern of B cells in TME. We observed B cells were distributed across different regions, manifesting in both clustered and dispersed patterns. Compared to features of B cells spatial distribution in CT region, B cells in IF region exhibited higher occupancy AUC (p = 0.00004), cluster density (p = 0.000002) and coverage ratio (p = 0.000884). Patients with longer survivals had smaller ΔFD (p = 0.05), higher B-cell cluster density (p = 0.003) and lower coverage ratio (p = 0.02) in IF region. Our study indicated the spatial distribution of B cells in IF and CT was different and the higher density of compact B-cell clusters in IF region may be associated with better prognosis in PDAC.

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