The Biogenesis, Biology, and Clinical Significance of Exosomal PD-L1 in Cancer

Tang, Yue; Zhang, Ping; Wang, Yumin; Wang, Jinpeng; Su, Min; Wang, Ying; Zhou, Lianqing; Zhou, Jinsong; Wang, Xiong; Zeng, Zhaoyang; Zhou, Yujuan; Nie, Shaolin; Liao, Qianjin

doi:10.3389/fimmu.2020.00604

Cited by 61 publications

(51 citation statements)

References 87 publications

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“…Moreover, there is crosstalk between IFN-γ and epidermal growth factor in the regulation of the distribution of ExoPD-L1 and cellular PD-L1 in breast cancer cells ( Monypenny et al, 2018 ). Recent studies have revealed that both cell-surface PD-L1 and ExoPD-L1 play crucial roles in immunosuppression, tumor progression, and response to cancer immunotherapy ( Zou et al, 2016 ; Chen G. et al, 2018 ; Theodoraki et al, 2018b ; Fan et al, 2019 ; Kim et al, 2019 ; Xie F. et al, 2019 ; Cordonnier et al, 2020 ; Huang et al, 2020 ; Tang et al, 2020 ). Nevertheless, the manner in which inflammatory cytokines affect PD-L1 expression on tumor cells and exosomes is still elusive ( Akbay et al, 2013 ; Chen et al, 2015 , 2019 ; Wang X. et al, 2017 ; Li et al, 2018 ; Lin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is important to provide individualized precise treatment and to predict tumor response to immunotherapy ( Madore et al, 2015 ; Kaunitz et al, 2017 ; Sui et al, 2018 ; Liu and Wu, 2019 ). To fulfill the need for real-time monitoring, the analysis of liquid biopsy-based circulating biomarkers is preferred ( Nishino et al, 2013 ; Ando et al, 2019 ; Gregg et al, 2019 ; Kloten et al, 2019 ; Tang et al, 2020 ). Recent studies demonstrated that melanoma patients who were less responsive to anti-PD-1 blockade had a significantly higher level of circulating ExoPD-L1 prior to treatment as compared with responders ( Chen G. et al, 2018 ).…”

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

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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Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

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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“…Chen et al recently showed that PD-L1 is enriched in exosomes, when compared with that in melanoma microvesicles, suggesting that exosomes are the primary source of PD-L1 among EVs in this cancer type (34). Other studies have confirmed exosomal PD-L1 in melanoma, prostate cancer, breast cancer, glioblastoma, head and neck cancer, lung cancer, and other tumors (35,36). However, the success of immunotherapy depends on the expression profile of these different ICPs.…”

Section: Checkpoint Inhibitor As a Contributor To Liquid Biopsymentioning

confidence: 99%

Extracellular Vesicles in Oncology: from Immune Suppression to Immunotherapy

Srivastava

Rathore

Munshi

et al. 2021

AAPS J

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Exosomes are involved in cell-to-cell communication and play a crucial role in cellular physiology. The role of exosomes in cancer has been widely explored. Tumor cells have evolved and adapted to evade the immune response. The study of the immune system’s modulations in favor of rogue tumor cells led to the development of a novel immunotherapeutic strategy targeting the immune checkpoint proteins (ICPs). In clinical settings, the response to ICP therapy has been inconsistent and is difficult to predict. Quantitating the targeted ICPs through immunohistochemistry is one approach, but is not pragmatic in a clinical setting and is often not sensitive. Examining the molecules present in bodily fluids to determine ICP treatment response, “liquid biopsy” is a convenient alternative. The term “liquid biopsy” refers to circulating tumor cells (CTCs), extracellular vesicles (EVs), non-coding (nc) RNA, circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), etc. EVs includes exosomes, microvesicles, and oncosomes. Herein, we focus on exosomes isolated from bodily fluids and their use in liquid biopsy. Due to their unique ability to transfer bioactive molecules and perturb the physiology of recipient cells, exosomes have garnered attention for their immune modulation role and as a resource to identify molecules associated with liquid biopsy–based diagnostic methods. In this review, we examine the putative role of exosomes and their cargo in influencing the immune system. We discuss the immune and tumor cells present in the tumor microenvironment (TME), and the exosomes derived from these cells to understand how they participate in creating the immune-suppressive TME. Additionally, use of exosomes in liquid biopsy–based methods to measure the treatment response elicited by immunotherapy is discussed. Finally, we describe how exosomes have been used to develop immune therapies, especially cell-free vaccines, for cancer treatment.

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“…Furthermore, Exos biologically functionalized by controlling source cells and downstream target cells. Self‐governing secretion of nucleic acids, proteins, and diverse cellular metabolites through Exos is vital for the differentiation and maturation of source cells and homeostasis (C. Hu et al, 2020; Y. Tang et al, 2020; Yue et al, 2020). Meanwhile, Exos can transport their genetic materials, such as DNA fragments, mRNAs, miRNAs, and long noncoding RNAs (lncRNAs), into target cells to modulate their genes and proteins expressions and to reinforce the activity of related pathways (Hashemian et al, 2020; Kwon et al, 2020; W. Wang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The potential roles of exosomal noncoding RNAs in osteosarcoma

Wang

2020

Journal Cellular Physiology

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Clinically, it is difficult to efficaciously screen and diagnose osteosarcoma (OS) in advance due to the low sensitivity and poor specificity of the existing tumor markers. Exosomes (Exos) are nanoscale vesicles containing RNAs, lipids, and proteins with a diameter of 30–100 nm. They are multivesicular bodies formed during the invagination of lysosomal particles in cells and released extracellularly after fusing with cell membranes. Besides, Exos are important carriers of cell‐to‐cell communication signals and genetic materials in the tumor microenvironment. During tumorigenesis, the tumor cells interplay with immune cells, endothelial cells, and related fibroblasts through Exos and boost cancer development. After altering the surrounding microenvironment, the Exos drive tumor cells to proliferate, speed up angiogenesis, and boost cancers to develop along with body fluid transportation. Currently, Exos are becoming novel noninvasive tumor diagnostic markers with high sensitivity, exerting pivotal impacts in fundamental research and clinical applications. Here, we review the existing literature on the roles of exosomal noncoding RNAs in OS progression and their potential clinical applications as novel biomarkers and therapeutics.

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The Biogenesis, Biology, and Clinical Significance of Exosomal PD-L1 in Cancer

Cited by 61 publications

References 87 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

Extracellular Vesicles in Oncology: from Immune Suppression to Immunotherapy

The potential roles of exosomal noncoding RNAs in osteosarcoma

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