RRC ID 68849
Author Kawana S, Saito R, Miki Y, Kimura Y, Abe J, Sato I, Endo M, Sugawara S, Sasano H.
Title Suppression of tumor immune microenvironment via microRNA-1 after epidermal growth factor receptor-tyrosine kinase inhibitor resistance acquirement in lung adenocarcinoma.
Journal Cancer Med
Abstract Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death-ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR-TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR-TKI resistance and lymphocyte infiltration, before and after acquiring EGFR-TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA-1 (miR-1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR-1 on EGFR-TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8-positive T cells were significantly decreased after development of EGFR-TKI resistance. In vitro studies revealed that miR-1 significantly inhibited EGFR-TKI effect and induction of cytokines, such as C-C motif chemokine ligand 5 and C-X-C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR-1 might suppress the TIME, following development of EGFR-TKI resistance. Therefore, miR-1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR-TKI resistance.
Volume 10(2)
Pages 718-727
Published 2021-1-1
DOI 10.1002/cam4.3639
PMID 33305905
PMC PMC7877390
MeSH Adenocarcinoma of Lung / drug therapy Adenocarcinoma of Lung / genetics Adenocarcinoma of Lung / immunology* Adenocarcinoma of Lung / pathology Aged Aged, 80 and over Biomarkers, Tumor / genetics Drug Resistance, Neoplasm* ErbB Receptors / antagonists & inhibitors Female Follow-Up Studies Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / drug therapy Lung Neoplasms / genetics Lung Neoplasms / immunology* Lung Neoplasms / pathology Male MicroRNAs / genetics* Middle Aged Prognosis Protein Kinase Inhibitors / pharmacology* Tumor Cells, Cultured Tumor Microenvironment / immunology*
IF 3.491
Human and Animal Cells PC-9(RCB4455)