In:
Pancreas, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 7 ( 2019-8), p. 904-912
Abstract:
Tumor-associated macrophages are dominant players in establishing the inmmunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC). Immune checkpoint inhibitor monotherapy has achieved limited clinical effectiveness. To date, the interaction of macrophages and checkpoint regulators and their correlation with clinicopathologic characteristics in PDAC have been largely unavailable. Methods Macrophages and immune checkpoint expression were assessed by immunohistochemistry from 80 PDAC samples. Clinicopathologic features and the prognostic value of each marker were evaluated. In vitro changes in the expression of immune markers in cocultured macrophages and PDAC cells were detected by Western blot and immunosorbance assays. Results The macrophages marker CD163 and the checkpoint marker programmed death-ligand 1 (PD-L1) remained as the independent prognostic factors for overall survival (hazard ratio, 2.543; P = 0.017 and hazard ratio, 2.389; P = 0.021). Furthermore, integrated analysis of CD163 and PD-L1 served as more optimal indicators of survival ( P = 0.000). In vitro coculture of macrophages and PDAC cells significantly increased the expression of CD163 and PD-L1, compared with monocultured counterpart ( P 〈 0.05). Conclusions Combined analysis of CD163 and PD-L1 was enhanced indicators of survival in PDAC patients. The interaction of macrophages and immune checkpoints implied the value of the combination therapy.
Type of Medium:
Online Resource
ISSN:
1536-4828
,
0885-3177
DOI:
10.1097/MPA.0000000000001364
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2053902-2
