In situ and dynamic screening of extracellular vesicles as predictive biomarkers in immune-checkpoint inhibitor therapies

被引：0

作者：

Wang, Yihe ^{[1
]}

Sun, Yue ^{[1
]}

Liu, Mengqi ^{[1
]}

Wang, Chao ^{[1
]}

Huang, Miao ^{[1
]}

Qiu, Jiaoyan ^{[1
]}

Yang, Ningkai ^{[1
]}

Zhang, Yu ^{[1
]}

Liu, Hong ^{[2
]}

Han, Lin ^{[1
,3
]}

机构：

[1] Shandong Univ, Inst Marine Sci & Technol, Tsingdao 266237, Peoples R China

[2] Shandong Univ, State Key Lab Crystal Mat, Jinan 250100, Peoples R China

[3] Shandong Engn Res Ctr Biomarker & Artificial Intel, Jinan 250100, Peoples R China

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2025年 / 23卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Extracellular vesicles; Tumor spheroids; Immune checkpoint inhibitors; PD-L1; Machine learning; T-CELLS; EXPRESSION; ROLES;

D O I：

10.1186/s12951-025-03467-y

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Extracellular vesicles (EVs) is promising in predicting the efficacy of immune checkpoint inhibitor (ICI) therapies. But it is challenging to determine the level of circulating EVs due to their variations in spatial and temporal distribution. To address this, we developed an in situ EV detection platform integrating multiplex EV capture with microfluidic-generated immune-tumor spheroids. This platform enables in situ monitoring of EV secretion dynamics under ICI and chemotherapeutic treatments, capturing localized and temporal changes in EV release. Using predictive models, we identified EVs carrying programmed cell death ligand 1 (PD-L1) as the most robust predictors of spheroid viability during treatment. RNA sequencing further revealed that dynamic EV expression changes are driven by gene transcription, providing a temporal understanding of EV regulation. Our platform overcomes the limitations of traditional methods by offering a physiologically relevant system to study EV-mediated immune responses. By addressing the spatial and temporal heterogeneity of EVs, this work advances EV-based biomarker discovery and provides a foundation for optimizing personalized immunotherapies.

引用

页数：15

共 53 条

[1] Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro [J].

Alessandri, Kevin ;

Sarangi, Bibhu Ranjan ;

Gurchenkov, Vasily Valerievitch ;

Sinha, Bidisha ;

Kiessling, Tobias Reinhold ;

Fetler, Luc ;

Rico, Felix ;

Scheuring, Simon ;

Lamaze, Christophe ;

Simon, Anthony ;

Geraldo, Sara ;

Vignjevic, Danijela ;

Domejean, Hugo ;

Rolland, Leslie ;

Funfak, Anette ;

Bibette, Jerome ;

Bremond, Nicolas ;

Nassoy, Pierre .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (37) :14843-14848

[2] Quantitative characterization of extracellular vesicle uptake and content delivery within mammalian cells [J].

Bonsergent, Emeline ;

Grisard, Eleonora ;

Buchrieser, Julian ;

Schwartz, Olivier ;

Thery, Clotilde ;

Lavieu, Gregory .

NATURE COMMUNICATIONS, 2021, 12 (01)

[3]

Chang WH, 2021, METHODS MOL BIOL, V2174, P143, DOI 10.1007/978-1-0716-0759-6_10

[4] Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response [J].

Chen, Gang ;

Huang, Alexander C. ;

Zhang, Wei ;

Zhang, Gao ;

Wu, Min ;

Xu, Wei ;

Yu, Zili ;

Yang, Jiegang ;

Wang, Beike ;

Sun, Honghong ;

Xia, Houfu ;

Man, Qiwen ;

Zhong, Wenqun ;

Antelo, Leonardo F. ;

Wu, Bin ;

Xiong, Xuepeng ;

Liu, Xiaoming ;

Guan, Lei ;

Li, Ting ;

Liu, Shujing ;

Yang, Ruifeng ;

Lu, Youtao ;

Dong, Liyun ;

McGettigan, Suzanne ;

Somasundaram, Rajasekharan ;

Radhakrishnan, Ravi ;

Mills, Gordon ;

Lu, Yiling ;

Kim, Junhyong ;

Chen, Youhai H. ;

Dong, Haidong ;

Zhao, Yifang ;

Karakousis, Giorgos C. ;

Mitchell, Tara C. ;

Schuchter, Lynn M. ;

Herlyn, Meenhard ;

Wherry, E. John ;

Xu, Xiaowei ;

Guo, Wei .

NATURE, 2018, 560 (7718) :382-+

[5] CD38-Mediated Immunosuppression as a Mechanism of Tumor Cell Escape from PD-1/PD-L1 Blockade [J].

Chen, Limo ;

Diao, Lixia ;

Yang, Yongbin ;

Yi, Xiaohui ;

Rodriguez, Leticia ;

Li, Yanli ;

Villalobos, Pamela A. ;

Cascone, Tina ;

Liu, Xi ;

Tan, Lin ;

Lorenzi, Philip L. ;

Huang, Anfei ;

Zhao, Qiang ;

Peng, Di ;

Fradette, Jared J. ;

Peng, David H. ;

Ungewiss, Christin ;

Roybal, Jonathon ;

Tong, Pan ;

Oba, Junna ;

Skoulidis, Ferdinandos ;

Peng, Weiyi ;

Carter, Brett W. ;

Gay, Carl M. ;

Fan, Youhong ;

Class, Caleb A. ;

Zhu, Jingfen ;

Rodriguez-Canales, Jaime ;

Kawakami, Masanori ;

Byers, Lauren Averett ;

Woodman, Scott E. ;

Papadimitrakopoulou, Vassiliki A. ;

Dmitrovsky, Ethan ;

Wang, Jing ;

Ullrich, Stephen E. ;

Wistuba, Ignacio I. ;

Heymach, John V. ;

Qin, F. Xiao-Feng ;

Gibbons, Don L. .

CANCER DISCOVERY, 2018, 8 (09) :1156-1175

[6] Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-κB [J].

Chow, Amy ;

Zhou, Weiying ;

Liu, Liang ;

Fong, Miranda Y. ;

Champer, Jackson ;

Van Haute, Desiree ;

Chin, Andrew R. ;

Ren, Xiubao ;

Gugiu, Bogdan Gabriel ;

Meng, Zhipeng ;

Huang, Wendong ;

Ngo, Vu ;

Kortylewski, Marcin ;

Wang, Shizhen Emily .

SCIENTIFIC REPORTS, 2014, 4

[7] Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients [J].

Cordonnier, Marine ;

Nardin, Charlee ;

Chanteloup, Gaetan ;

Derangere, Valentin ;

Algros, Marie-Paule ;

Arnould, Laurent ;

Garrido, Carmen ;

Aubin, Francois ;

Gobbo, Jessica .

JOURNAL OF EXTRACELLULAR VESICLES, 2020, 9 (01)

[8] Immune checkpoint inhibitors: recent progress and potential biomarkers [J].

Darvin, Pramod ;

Toor, Salman M. ;

Nair, Varun Sasidharan ;

Elkord, Eyad .

EXPERIMENTAL AND MOLECULAR MEDICINE, 2018, 50 :1-11

[9] Predictive biomarkers for checkpoint inhibitor-based immunotherapy [J].

Gibney, Geoffrey T. ;

Weiner, Louis M. ;

Atkins, Michael B. .

LANCET ONCOLOGY, 2016, 17 (12) :E542-E551

[10] Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia [J].

Grist, Samantha M. ;

Nasseri, S. Soroush ;

Laplatine, Loic ;

Schmok, Jonathan C. ;

Yao, Dickson ;

Hua, Jessica ;

Chrostowski, Lukas ;

Cheung, Karen C. .

SCIENTIFIC REPORTS, 2019, 9 (1)

← 1 2 3 4 5 6 →