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

Xiaocui Li, Guijun He, Jican Liu, Meizhu Yan, Manru Shen, Linfang Xu, Min An, Jiying Huang, Zhenjun Gao

International immunopharmacology 2022 May

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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. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Xiaocui Li, Guijun He, Jican Liu, Meizhu Yan, Manru Shen, Linfang Xu, Min An, Jiying Huang, Zhenjun Gao. CCL2-mediated monocytes regulate immune checkpoint blockade resistance in pancreatic cancer. International immunopharmacology. 2022 May;106:108598