Pulmonary Aerosol Delivery of Let-7b microRNA Confers a Striking Inhibitory Effect on Lung Carcinogenesis through Targeting the Tumor Immune Microenvironment.
Adv Sci (Weinh)
; 8(17): e2100629, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34236760
ABSTRACT
MicroRNAs are potential candidates for lung cancer prevention and therapy. A major limitation is the lack of an efficient delivery system to directly deliver miRNA to cancer cells while limiting systemic exposure. The delivery of miRNA via inhalation is a potential strategy for lung cancer prevention in high-risk individuals. In this study, the authors investigate the efficacy of aerosolized let-7b miRNA treatment in lung cancer prevention. Let-7b shows significant inhibition of B[a]P-induced lung adenoma with no detectable side effects. Single-cell RNA sequencing of tumor-infiltrating T cells from primary tumors reveals that Let-7b post-transcriptionally suppresses PD-L1 and PD-1 expression in the tumor microenvironment, suggesting that let-7b miRNAs may promote antitumor immunity in vivo. Let-7b treatment decreases the expression of PD-1 in CD8+ T cells and reduces PD-L1 expression in lung tumor cells. The results suggest that this aerosolized let-7b mimic is a promising approach for lung cancer prevention, and that the in vivo tumor inhibitory effects of let-7b are mediated, at least in part, by immune-promoting effects via downregulating PD-L1 in tumors and/or PD-1 on CD8+ T cells. These changes potentiate antitumor CD8+ T cell immune responses, and ultimately lead to tumor inhibition.
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Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Microambiente Tumoral
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Carcinogênese
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article