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

•CCL2 induces monocyte infiltration in pancreatic cancer;•CCL2 blockade affects the pancreatic tumor microenvironment;•CCL2 signaling blockade enhances the efficacy of immune checkpoint inhibition;•Antitumor effect of anti-PD1 antibody and CCL2 blockade is CD8-dependent. The immunosuppressive microe...

Full description

Saved in:
Bibliographic Details
Published in:International immunopharmacology 2022-05, Vol.106, p.108598-108598, Article 108598
Main Authors: Li, Xiaocui, He, Guijun, Liu, Jican, Yan, Meizhu, Shen, Manru, Xu, Linfang, An, Min, Huang, Jiying, Gao, Zhenjun
Format: Article
Language:English
Subjects:
Adenocarcinoma
CCL2
CD8 antigen
Chemokine CCL2
Chemokines
Drug Resistance, Neoplasm
Humans
Immune checkpoint
Immune Checkpoint Inhibitors - therapeutic use
Immunosuppression
Immunotherapy
Ligands
Lymphocytes
Lymphocytes T
Metastases
Microenvironments
Monocyte chemoattractant protein 1
Monocytes
Neutralization
Pancreatic cancer
Pancreatic ductal adenocarcinoma
Pancreatic Neoplasms
Tumor Microenvironment
Tumorigenesis
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•CCL2 induces monocyte infiltration in pancreatic cancer;•CCL2 blockade affects the pancreatic tumor microenvironment;•CCL2 signaling blockade enhances the efficacy of immune checkpoint inhibition;•Antitumor effect of anti-PD1 antibody and CCL2 blockade is CD8-dependent. 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.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2022.108598