High intensity focused ultrasound enhances anti-tumor immunity by inhibiting the negative regulatory effect of miR-134 on CD86 in a murine melanoma model.
HIFU has been demonstrated to enhance anti-tumor immunity, however, the mechanism of which has not been well elucidated. Emerging evidence indicates that miRNAs play important roles in immune response. In this study, we used the B16F10 melanoma allograft mouse model to investigate the role of miRNAs in HIFU-enhanced anti-tumor immunity. We found that HIFU treatment decreased circulating B16F10 cells and pulmonary metastasis nodules while increased IFN-γ and TNF-α in the peripheral blood and cumulative mouse survival, which was associated with inhibition of miR-134 expression and activation of CD86 expression in tumor tissues. Further, we determined that miR-134 directly binds to the 3'UTR of CD86 mRNA to suppress its expression in B16F10 cells. When B16F10 cells transfected with miR-134 were co-cultured with normal splenic lymphocytes, the secretion of IFN-γ and TNF-α from lymphocytes was reduced and B16F10 cell survival was increased. HIFU exposure efficiently decreased miR-134 while increased CD86 expression in B16F10 cells in vitro. CD86 knockdown with siRNA markedly rescued the viability of HIFU-treated B16F10 cells that co-cultured with lymphocytes. Altogether, our results suggest that HIFU down-regulates miR-134 to release the inhibition of miR-134 on CD86 in melanoma cells, thereby enhancing anti-tumor immune response.
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Shi-Mei
SM
Yuan
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Huan
H
Li
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Min
M
Yang
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
He
H
Zha
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Hui
H
Sun
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Xue-Ru
XR
Li
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Ai-Fang
AF
Li
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Yue
Y
Gu
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Liang
L
Duan
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Jin-Yong
JY
Luo
State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Chong-Yan
CY
Li
State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Yan
Y
Wang
State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Zhi-Biao
ZB
Wang
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.|Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
Tong-Chuan
TC
He
Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Lan
L
Zhou
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D051940:B7-2 Antigen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics / Q000528:radiation effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology* / Q000556:secondary; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy; D014463:Ultrasonography; D023041:Xenograft Model Antitumor Assays
D051940:B7-2 Antigen; C497964:CD86 protein, human; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
HIFU; anti-tumor immunity; co-stimulatory molecules; microRNA