CCL2-mediated monocytes regulate immune checkpoint blockade resistance in pancreatic cancer

被引:9
作者
Li, Xiaocui [1 ]
He, Guijun [1 ]
Liu, Jican [2 ]
Yan, Meizhu [1 ]
Shen, Manru [1 ]
Xu, Linfang [1 ]
An, Min [1 ]
Huang, Jiying [1 ]
Gao, Zhenjun [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Gastroenterol, QingPu Branch, 1158 Pk Rd E, Shanghai 201700, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Dept Pathol, QingPu Branch, Shanghai 201700, Peoples R China
关键词
Pancreatic ductal adenocarcinoma; CCL2; Monocytes; Immunosuppression; Immunotherapy; ANTI-PD-L1; ANTIBODY; CHEMOATTRACTANT; IMMUNOTHERAPY; PROTEIN-1; CELLS;
D O I
10.1016/j.intimp.2022.108598
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immunosuppressive microenvironment of pancreatic ductal adenocarcinoma (PDAC) contributes to resistance to immune checkpoint blockade. C-C motif chemokine ligand 2 (CCL2) is believed to participate in pancreatic tumorigenesis, but its role in PDAC progression and resistance to immune checkpoint blockade remains unclear. We hypothesized that CCL2 contributes to the pancreatic immunosuppressive microenvironment. In this study, we found that CCL2 recruits monocytes to and decrease CD8+ T cell infiltration in pancreatic tumors. CCL2 inhibition and monocyte neutralization increased the sensitivity of PDAC to immune checkpoint blockade. The findings of our study suggest the potential of CCL2-mediated monocytes as a target for PDAC treatment.
引用
收藏
页数:8
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