Chimeric antigen receptor-modified macrophages trigger systemic anti-tumour immunity.
Zhiyuan NiuGuanxu ChenWei ChangPengyang SunZhixia LuoHuiyong ZhangLingtong ZhiChangjiang GuoHan ChenMeichen YinWuling ZhuPublished in: The Journal of pathology (2020)
Preliminary results and emerging data have shown that lipid droplet high (LDhi ) immunosuppressive cells accumulate in tumour tissues. By tracking and phenotypic profiling of LDhi cells, we find that LDhi CD19+ , LDhi CD11b+ , and LDhi Ly6G+ immune cell populations appear in the spleen, thymus, and tumour tissues in a syngeneic tumour model. Using a contact-dependent reporter system, we discover a LDhi CCR7hi immunosuppressive cell population that migrates from tumour tissues to the spleen and thymus. Hence, we engineered a family of chimeric antigen receptor-modified macrophages (CAR-Ms) that direct macrophages to CCR7-positive cells and show that the cytosolic domain from Mer receptor tyrosine kinase (MerTK) triggers tumour cell cytotoxicity by the CAR-Ms. In vivo, CCR7-targeted CAR-Ms suppressed tumour growth and prolonged survival by preventing metastasis and by inducing systemic anti-tumour immunity through retarding the migration of LDhi CCR7hi immunosuppressive cells from tumour tissues to distal immune organs, indicating an important role for CCR7 in tumour cell-induced immune tolerance. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Keyphrases
- single cell
- induced apoptosis
- tyrosine kinase
- gene expression
- dendritic cells
- mass spectrometry
- regulatory t cells
- multiple sclerosis
- randomized controlled trial
- cell cycle arrest
- cell therapy
- stem cells
- systematic review
- high throughput
- oxidative stress
- bone marrow
- artificial intelligence
- endothelial cells
- cell proliferation
- fatty acid
- nk cells