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Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer

Cited 196 time in Web of Science Cited 158 time in Scopus
Authors

Kim, Dong Ha; Kim, HyeongRyul; Choi, Yun Jung; Kim, Seon Ye; Lee, Jung-Eun; Sung, Ki Jung; Sung, Young Hoon; Packd, Chan-Gi; Jung, Min-kyo; Han, Buhm; Kim, Kunhee; Kim, Woo Sung; Nam, Soo Jeong; Choi, Chang-Min; Yun, Miyong; Lee, Jae Cheol; Rho, Jin Kyung

Issue Date
2019-08
Publisher
생화학분자생물학회
Citation
Experimental and Molecular Medicine, Vol.51 No.8, p. 94
Abstract
Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway blockade is a promising new cancer therapy. Although PD-1/PD-L1 treatment has yielded clinical benefits in several types of cancer, further studies are required to clarify predictive biomarkers for drug efficacy and to understand the fundamental mechanism of PD-1/PD-L1 interaction between host and tumor cells. Here, we show that exosomes derived from lung cancer cells express PD-L1 and play a role in immune escape by reducing T-cell activity and promoting tumor growth. The abundance of PD-L1 on exosomes represented the quantity of PD-L1 expression on cell surfaces. Exosomes containing PD-L1 inhibited interferon-gamma (IFN-gamma) secretion by Jurkat T cells. IFN-gamma secretion was restored by PD-L1 knockout or masking on the exosomes. Both forced expression of PD-L1 on cells without PD-L1 and treatment with exosomes containing PD-L1 enhanced tumor growth in vivo. PD-L1 was present on exosomes isolated from the plasma of patients with non-small cell lung cancer, and its abundance in exosomes was correlated with PD-L1 positivity in tumor tissues. Exosomes can impair immune functions by reducing cytokine production and inducing apoptosis in CD8(+) T cells. Our findings indicate that tumor-derived exosomes expressing PD-L1 may be an important mediator of tumor immune escape.
ISSN
1226-3613
URI
https://hdl.handle.net/10371/191501
DOI
https://doi.org/10.1038/s12276-019-0295-2
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Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
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