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

Huang, Mengjiao; Yang, Juanjuan; Wang, Teng; Song, Jia; Xia, Jinglu; Wu, Lingling; Wang, Wei; Wu, Qiaoyi; Zhu, Zhi; Song, Yanling; Yang, Chaoyong

doi:10.1002/ange.201916039

Cited by 49 publications

(55 citation statements)

References 40 publications

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“…Several studies revealed the presence of PD-L1 in exosomes isolated from blood samples of patients with cancer, and the level of PD-L1 correlates with pathological features of these patients [23,24,39,40]. Chen et al reported metastatic melanomas released exosomes, delivering PD-L1 on their surface.…”

Section: Discussionmentioning

confidence: 99%

Exosomal PD-L1 Derived From Osteosarcoma is Associated With Pulmonary Metastasis for Patients With Osteosarcoma

Wang¹,

Zhang²,

Sun³

et al. 2020

Preprint

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Abstract Background Recent studies indicated that exosomal programmed death-ligand 1 (PD-L1) derived from cancers could induce immunosuppression and tumor pathogenesis. However, it is unclear how the exosome influences the osteosarcoma (OS) progression and whether PD-L1 also exists in serum exosomes (Sr-exosomes) of patients with osteosarcoma. Methods We examined serum exosomes from 70 patients with osteosarcoma, 9 patients with benign tumors and 22 healthy donors. Osteosarcoma-derived exosomes and exosomal-PD-L1 were functionally evaluated using in vivo and in vitro models. Results The characteristics of serum exosomes of OS patients and OS cell line exosomes were confirmed by several methods. Bioinformatic analysis demonstrated that Sr-exosomes isolated from OS patients may involve in the important process of immune function and cancer pathogenesis for OS patients. Meanwhile, exosomes derived from OS cell line and serum of OS patients could induce osteosarcoma migration and invision in vitro. Then, we confirmed PD-L1 existing in Sr-exosomes of patients with osteosarcoma and higher level of Sr-exosomal PD-L1 in OS patients compared to healthy donors and patients with benign tumor. Furthermore, exosomal-PD-L1 derived from osteosarcoma promoted the pulmonary metastasis, which was demonstrated in the osteosarcoma metastatic model. Conclusion We confirm that osteosarcoma releases the exosomes carrying PD-L1 on their surface and induces the pathogenesis of pulmonary metastasis for OS patients.

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Section: Discussionmentioning

confidence: 99%

Exosomal PD-L1 Derived From Osteosarcoma is Associated With Pulmonary Metastasis for Patients With Osteosarcoma

Wang¹,

Zhang²,

Sun³

et al. 2020

Preprint

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“…However, there are pitfalls of using cellular PD-L1 such as traumatic biopsy, missing small tumors, heterogeneity of PD-L1 expression within tumors, unavailability of dynamic observation, and limited sensitivity ( Kaunitz et al, 2017 ; Bassanelli et al, 2018 ; Teixido et al, 2018 ; Davis and Patel, 2019 ; Stovgaard et al, 2019 ; Xu G. et al, 2019 ). Recent studies indicate that circulating ExoPD-L1 is emerging as a non-invasive and readily available biomarker, and is more easily detectable and reliable than both tissue and soluble PD-L1 in plasma ( Liu et al, 2018b ; Cordonnier et al, 2020 ; Huang et al, 2020 ; Pang et al, 2020 ).…”

Section: Potential Clinical Implication Of Circulating Exopd-l1 As a mentioning

confidence: 99%

“…However, in melanoma, the level of ExoPD-L1 in the blood, rather than the number and total protein content of exosomes, is elevated in metastatic melanoma patients compared with healthy subjects ( Chen G. et al, 2018 ). Furthermore, patients with NSCLC and adenocarcinoma also exhibit higher levels of circulating ExoPD-L1 compared with healthy controls ( Liu et al, 2018b ; Li et al, 2019a ; Huang et al, 2020 ; Pang et al, 2020 ). Therefore, circulating ExoPD-L1 may be a potential diagnostic marker.…”

Section: Potential Clinical Implication Of Circulating Exopd-l1 As a mentioning

confidence: 99%

“…Therefore, circulating ExoPD-L1 may be a potential diagnostic marker. In addition, high levels of circulating ExoPD-L1 were associated with metastatic melanoma, advanced HNSCC, and poor prognosis in pancreatic cancer, further indicating that circulating ExoPD-L1 may be a useful biomarker for tumor progression ( Theodoraki et al, 2018a ; Lux et al, 2019 ; Huang et al, 2020 ).…”

Section: Potential Clinical Implication Of Circulating Exopd-l1 As a mentioning

confidence: 99%

“…Increasing evidence indicates that exosomes derived from tumor cells can regulate the tumor microenvironment and promote cancer progression via their cargos, which include proteins, lipids, and nucleic acids ( Anastasiadou and Slack, 2014 ; Lazaro-Ibanez et al, 2019 ; Zhang and Yu, 2019 ; Raimondo et al, 2020 ; Sahebi et al, 2020 ). Recent studies have demonstrated that PD-L1 also exists on the surface of exosomes generated by their parental tumor cells ( Chen G. et al, 2018 ; Lubin et al, 2018 ; Ricklefs et al, 2018 ; Theodoraki et al, 2018b ; Yang et al, 2018 ; Fan et al, 2019 ; Kim et al, 2019 ; Poggio et al, 2019 ; Cordonnier et al, 2020 ; Huang et al, 2020 ). Moreover, ExoPD-L1 can function as efficiently as PD-L1 on the tumor cell surface through direct ligation to PD-1 on the surface of lymphocytes in tumor foci ( Chen G. et al, 2018 ; Lubin et al, 2018 ; Ricklefs et al, 2018 ; Theodoraki et al, 2018b ; Yang et al, 2018 ; Fan et al, 2019 ; Kim et al, 2019 ; Poggio et al, 2019 ; Cordonnier et al, 2020 ; Huang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies

Zhou

Guo

et al. 2020

Front. Cell Dev. Biol.

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As a classical immune checkpoint molecule, PD-L1 on the surface of tumor cells plays a pivotal role in tumor immunosuppression, primarily by inhibiting the antitumor activities of T cells by binding to its receptor PD-1. PD-1/PD-L1 inhibitors have demonstrated unprecedented promise in treating various human cancers with impressive efficacy. However, a significant portion of cancer patients remains less responsive. Therefore, a better understanding of PD-L1-mediated immune escape is imperative. PD-L1 can be expressed on the surface of tumor cells, but it is also found to exist in extracellular forms, such as on exosomes. Recent studies have revealed the importance of exosomal PD-L1 (ExoPD-L1). As an alternative to membrane-bound PD-L1, ExoPD-L1 produced by tumor cells also plays an important regulatory role in the antitumor immune response. We review the recent remarkable findings on the biological functions of ExoPD-L1, including the inhibition of lymphocyte activities, migration to PD-L1-negative tumor cells and immune cells, induction of both local and systemic immunosuppression, and promotion of tumor growth. We also discuss the potential implications of ExoPD-L1 as a predictor for disease progression and treatment response, sensitive methods for detection of circulating ExoPD-L1, and the novel therapeutic strategies combining the inhibition of exosome biogenesis with PD-L1 blockade in the clinic.

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Thermophoretic Assay for Biosensing

Ling,

Yuan,

Chen

et al. 2024

Adv Materials Technologies

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Thermophoresis refers to the directional movement of particles driven by temperature gradients, which is ubiquitous in nature. This phenomenon can be conveniently used to manipulate molecules and objects such as biomolecules, colloids, metal nanoparticles, and cells. Because of these advantages, thermophoresis is widely used in biosensing. In vitro diagnosis, as an important field of biosensing, is highly compatible with thermophoresis. Compared with traditional in vitro diagnostic techniques, thermophoretic diagnosis is a homogeneous system that boasts high efficiency and rapid detection as well as a wide detection range; thus, thermophoresis has a myriad of applications. The emergence of microscale and multifield coupling thermophoresis technologies yield widespread applications of thermophoresis in the field of in vitro diagnostics. This study presents the history of thermophoresis and reviews various cases of biosensors utilizing thermophoresis. Those biosensors are widely used in in vitro diagnostics, biomarker discovery, and other fields. Furthermore, it assesses the advantages of thermophoresis, and finally discusses its current challenges and future development.

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

Cited by 49 publications

References 40 publications

Exosomal PD-L1 Derived From Osteosarcoma is Associated With Pulmonary Metastasis for Patients With Osteosarcoma

Exosomal PD-L1 Derived From Osteosarcoma is Associated With Pulmonary Metastasis for Patients With Osteosarcoma

Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies

Thermophoretic Assay for Biosensing

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