Volume 59, Issue 12 pp. 4800-4805
Research Article

Homogeneous, Low-volume, Efficient, and Sensitive Quantitation of Circulating Exosomal PD-L1 for Cancer Diagnosis and Immunotherapy Response Prediction

Mengjiao Huang

Mengjiao Huang

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 China

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Dr. Juanjuan Yang

Dr. Juanjuan Yang

College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350002 China

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Teng Wang

Teng Wang

College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350002 China

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Dr. Jia Song

Dr. Jia Song

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Jinglu Xia

Jinglu Xia

College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350002 China

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Dr. Lingling Wu

Dr. Lingling Wu

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Dr. Wei Wang

Dr. Wei Wang

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Dr. Qiaoyi Wu

Dr. Qiaoyi Wu

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 China

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Prof. Zhi Zhu

Prof. Zhi Zhu

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 China

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Dr. Yanling Song

Corresponding Author

Dr. Yanling Song

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 China

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Prof. Chaoyong Yang

Corresponding Author

Prof. Chaoyong Yang

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 China

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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First published: 08 January 2020
Citations: 197

Graphical Abstract

An aptamer-induced thermophoresis quantitation of exosomal programmed death-ligand 1 (PD-L1, a transmembrane protein) was developed, which integrates effective recognition of aptamer and homogeneous thermophoresis. The facile technique is more sensitive and efficient than the current enzyme-linked immunosorbent assay (ELISA)-based methods. Translation of the method into standard clinical practice for immunotherapy prediction and monitoring is anticipated.

Abstract

Immunotherapy has revolutionized cancer treatment, but its efficacy is severely hindered by the lack of effective predictors. Herein, we developed a homogeneous, low-volume, efficient, and sensitive exosomal programmed death-ligand 1 (PD-L1, a type of transmembrane protein) quantitation method for cancer diagnosis and immunotherapy response prediction (HOLMES-ExoPD-L1). The method combines a newly evolved aptamer that efficiently binds to PD-L1 with less hindrance by antigen glycosylation than antibody, and homogeneous thermophoresis with a rapid binding kinetic. As a result, HOLMES-ExoPD-L1 is higher in sensitivity, more rapid in reaction time, and easier to operate than existing enzyme-linked immunosorbent assay (ELISA)-based methods. As a consequence of an outstanding improvement of sensitivity, the level of circulating exosomal PD-L1 detected by HOLMES-ExoPD-L1 can effectively distinguish cancer patients from healthy volunteers, and for the first time was found to correlate positively with the metastasis of adenocarcinoma. Overall, HOLMES-ExoPD-L1 brings a fresh approach to exosomal PD-L1 quantitation, offering unprecedented potential for early cancer diagnosis and immunotherapy response prediction.

Conflict of interest

The authors declare no conflict of interest.

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