BACKGROUND

Immune checkpoint blockade has emerged as a potential cancer immunotherapy. The "don't eat me" signal in cancer cells binds signal regulatory protein-α on macrophages and prevents their phagocytosis. The role of miR-340 in pancreatic ductal adenocarcinoma (PDAC), especially in tumor immunity, has not been explored. Here, we examined the clinical and biological relevance of miR-340 and the molecular pathways regulated by miR-340 in PDAC.

METHODS

and miR-340 expression and the relationship with cancer patient survival were analyzed by bioinformatics. The mechanism of miR-340 action was explored through bioinformatics, luciferase reporter, qRT-PCR and western blot analyses. The effects of miR-340 on cancer cells were analyzed in terms of apoptosis, proliferation, migration and phagocytosis by macrophages. tumorigenesis was studied in orthotopic and subcutaneous models, and immune cells from the peripheral and tumor immune microenvironments were analyzed by flow cytometry. Depletion of macrophages was used to verify the role of macrophages in impacting the function of miR-340 in tumor progression.

RESULTS

miR-340 directly regulates and inversely correlates with and it predicts patient survival in PDAC. The restoration of miR-340 expression in pancreatic cancer cells was sufficient to downregulate and promote phagocytosis of macrophages, further inhibiting tumor growth. The overexpression of miR-340 promoted macrophages to become M1-like phenotype polarized in peripheral and tumor immune microenvironments and increased T cells, especially CD8 T cells, contributing to the antitumor effect of miR-340.

CONCLUSIONS

miR-340 is a key regulator of phagocytosis and antitumor immunity, and it could offer a new opportunity for immunotherapy for PDAC.