Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.572689
Keywords
gastric cancer; M1 macrophage; microRNA-16-5p; T cell immune response; PD-L1
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Funding
- First Affiliated Hospital of Harbin Medical University [2019B21]
- National Natural Science Foundation of China Youth Found [81600492]
- Supporting Project for Outstanding Young Medical Talents of the First Affiliated Hospital of Harbin Medical University [HYD2020JQ0011]
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Macrophages have an affinity to developing tumors and have been shown to play a role in tumor combat and immune surveillance. However, the exact mechanism by which macrophages participate in the anti-tumor immune response remains unclear. Hence, the current study aimed to identify the effect of macrophages on gastric cancer (GC) cells via exosomes. Paired cancerous, tumor-adjacent, and non-cancerous stomach tissues were initially from 68 GC patients. T cells were isolated from peripheral blood mononuclear cells (PBMCs) obtained from both the GC patients as well as the healthy donors. Next, the exosomes were isolated from LPS and IFN-gamma-induced PBMCs (M1 macrophages) and co-cultured with human GC cells. Another co-culture system comprised of CD3(+) T cells and exosomes-treated GC cells was then performed. BALB/c mice and NOD/SCID nude mice were prepared for effects of exosomal miR-16-5p on tumor growth and anti-tumor immune response in GC in vivo. A relationship between M1 macrophages and the poor survival of GC patients was identified, while they secreted exosomes to inhibit GC development and activate a T cell-dependent immune response. Our results revealed that miR-16-5p was transferred intercellularly from M1 macrophages to GC cells via exosomes and targeted PD-L1. M1 macrophage-derived exosomes containing miR-16-5p were found to trigger a T cell immune response which inhibited tumor formation both in vitro and in vivo by decreasing the expression of PD-L1. Taken together, the key findings of the current study suggest that M1 macrophage-derived exosomes carrying miR-16-5p exert an inhibitory effect on GC progression through activation of T cell immune response via PD-L1. Our study highlights the promise of M1 macrophages as a potential cell-based therapy for GC treatment by increasing miR-16-5p in exosomes.
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