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/anie.201916039

Cited by 164 publications

(175 citation statements)

References 41 publications

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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: Exopd-l1 As a Biomarker For Diagnosis And Disease Progressionmentioning

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: Exopd-l1 As a Biomarker For Diagnosis And Disease Progressionmentioning

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%

“…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). Surprisingly, although the cell-surface PD-L1 is low or absent, the ExoPD-L1 may be highly secreted by its parental tumor cells that are resistant to anti-PD-L1 therapy (Poggio et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

confidence: 99%

Section: Exopd-l1 As a Biomarker For Diagnosis And Disease Progressionmentioning

confidence: 99%

Section: Exopd-l1 As a Biomarker For Diagnosis And Disease Progressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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EVs‐on‐a‐Bubble: Self‐Aggregated Click Bubbles Streamline Isolation and Amplified Profiling of Circulating Extracellular Vesicles

Wei,

Xiang,

Qin

et al. 2023

Adv Funct Materials

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Tumor‐derived circulating extracellular vesicles (EVs) provide a non‐invasive solution for cancer diagnostics, but hampered by challenges in EVs isolation and profiling. Herein, this work shows that bioorthogonal microbubbles (click bubbles) combine a panel of fluorescent aptamers for streamlined isolation and profiling of oncologic EVs in a single assay. This click bubble‐driven aptasensor (cBAS) features self‐aggregation, self‐separation and self‐enhancing in fluorescence. The facile protein phase transition renders bubble surface polyvalent with rich clickable motifs, enabling fast enrichment of EVs. Moreover, the buoyancy allows click bubbles to self‐float to the droplet apex for self‐aggregated fluorescence enhancement via a bubble lensing effect, thus achieving a sensitive profiling of EVs without requiring additional signal amplification or ultrasensitive detectors. By using cBAS to profile EVs surface proteins from a cohort (n = 45) across three cancer types, a machine learning algorithm enables cancer diagnosis and classification with an overall accuracy of 91%. This EVs‐on‐a‐bubble assay is fast, sensitive, self‐powered, and provides a promising tool to facilitate EVs‐based cancer diagnosis in clinical settings.

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A Versatile Design‐Enabled Analysis of Circulating Extracellular Vesicles in Disease Diagnosis

Liu

Yao

Huang

et al. 2023

Adv Healthcare Materials

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Circulating extracellular vesicles (EVs) are considered as potential biomarkers for treatment and diagnosis of many diseases. Most of the existing methods for the EV analysis only have a single function and thus reveal limited information carried by EVs. Herein, a phosphatidylserine-targeting peptide-facilitated design that enables the versatile analysis of circulating EVs for varying requirement is proposed. In the design, DNA probes are inserted into the EV membrane through hydrophobic interactions, and accelerate the removal of protective shielding from DNA-gated metal-organic framework, thereby releasing a large number of methylene blue molecules to amplify the electrochemical signal. Electrochemical results demonstrate equally high sensitivities toward the quantification of EVs derived from different cell sources using an indiscriminative DNA probe. More importantly, the probe can be endowed with extended function for more accurate classification of cell-specific features through the identification of specific EV biomarkers, and demonstrates the potential use in the diagnosis of cardiovascular in a principle-of-proof study for clinical application. Therefore, the method provides a versatile design for the identification of EV features, and may address the needs of clinical diagnosis in the future.

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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 164 publications

References 41 publications

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

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

EVs‐on‐a‐Bubble: Self‐Aggregated Click Bubbles Streamline Isolation and Amplified Profiling of Circulating Extracellular Vesicles

A Versatile Design‐Enabled Analysis of Circulating Extracellular Vesicles in Disease Diagnosis

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