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Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer
Dong Ha Kim,HyeongRyul Kim,Yun Jung Choi,Seon Ye Kim,Jung Eun Lee,Ki Jung Sung,Young Hoon Sung,Chan-Gi Pack,Min Kyo Jung,Buhm Han,Kunhee Kim,Woo Sung Kim,Soo Jeong Nam,Chang Min Choi,Miyong Yun,Jae Ch 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
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-γ) secretion by Jurkat T cells. IFN-γ 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.
Rahim, Muhammad Kashif,Kim, Sung Eun,So, Hyeongryul,Kim, Hyung Jun,Cheon, Gi Jeong,Lee, Eun Seong,Kang, Keon Wook,Lee, Dong Soo 大韓核醫學會 2014 핵의학 분자영상 Vol.48 No.1
<P>Image quantification studies in positron emission tomography/computed tomography (PET/CT) are of immense importance in the diagnosis and follow-up of variety of cancers. In this review we have described the current image quantification methodologies employed in (18)F-fluorodeoxyglucose ((18)F-FDG) PET in major oncological conditions with particular emphasis on tumor heterogeneity studies. We have described various quantitative parameters being used in PET image analysis. The main contemporary methodology is to measure tumor metabolic activity; however, analysis of other image-related parameters is also increasing. Primarily, we have identified the existing role of tumor heterogeneity studies in major cancers using (18)F-FDG PET. We have also described some newer radiopharmaceuticals other than (18)F-FDG being studied/used in the management of these cancers. Tumor heterogeneity studies are being performed in almost all major oncological conditions using (18)F-FDG PET. The role of these studies is very promising in the management of these conditions.</P>