Department of Gastroenterology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China.
Department of Pathology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China.
Int Immunopharmacol. 2022 May;106:108598. doi: 10.1016/j.intimp.2022.108598. Epub 2022 Feb 17.
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.
胰腺导管腺癌 (PDAC) 的免疫抑制微环境导致对免疫检查点阻断的抵抗。趋化因子配体 2 (CCL2) 被认为参与了胰腺肿瘤的发生，但它在 PDAC 进展和对免疫检查点阻断的抵抗中的作用仍不清楚。我们假设 CCL2 有助于胰腺免疫抑制微环境。在这项研究中，我们发现 CCL2 募集单核细胞并减少胰腺肿瘤中 CD8 T 细胞的浸润。CCL2 抑制和单核细胞中和增加了 PDAC 对免疫检查点阻断的敏感性。我们的研究结果表明，CCL2 介导的单核细胞作为 PDAC 治疗靶点的潜力。
