The role of exosomal PD-L1 in tumor progression and immunotherapy

Xie, Feiting; Xu, Mengxue; Lü, Jian; Mao, Lingxiang; Wang, Shengjun

doi:10.1186/s12943-019-1074-3

Cited by 273 publications

(239 citation statements)

References 92 publications

(84 reference statements)

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“…In this context, it is also noteworthy, that there exists a broad distribution of PD-L1 in different cellular compartments [24]. These formats include not only membranous PD-L1 (mPD-L1) [25], but also cytoplasmic PD-L1 (cPD-L1) [26,27], nuclear PD-L1 (nPD-L1) [28], serum PD-L1 (sPD-L1) [29] and exosomal PD-L1 [30].…”

Section: Characteristics Of the Pd1 Ligands Pd-l1 And Pd-l2mentioning

confidence: 98%

Basis of PD1/PD-L1 Therapies

Seliger

2019

JCM

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It is obvious that tumor cells have developed a number of strategies to escape immune surveillance including an altered expression of various immune checkpoints, such as the programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2. The interaction between PD-1 and PD-L1 results in an activation of self-tolerance pathways in both immune cells as well as tumor cells. Thus, these molecules represent excellent targets for T cell-based immunotherapies. However, the efficacy of therapies using checkpoint inhibitors is variable and only a limited number of patients receive a long-term response, while others develop resistances. Therefore, a better insight into the constitutive expression levels and their control as well as the predictive and prognostic value of PD-1/PD-L1, which are controversially discussed due to the methodological assessment, the dynamic and time-related variable expression of these molecules, is urgently required. In this review, the current knowledge of the PD-L1 and PD-1 genes, their expression in immune and tumor cells, the underlying molecular mechanisms of their regulation and their association with clinical parameters and therapy responses are summarized.

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Section: Characteristics Of the Pd1 Ligands Pd-l1 And Pd-l2mentioning

confidence: 98%

Basis of PD1/PD-L1 Therapies

Seliger

2019

JCM

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“…Exosomes from melanoma cells also take part in the immune-escape, either directly inhibiting immune effector cells or indirectly stimulating regulatory cells. The direct modulation of immune cells largely occurs in response to melanoma Exo-related inhibitory or pro-apoptotic signals and are mostly related to the exosomal expression of PD-L1 [32], while the indirect way involves the up-regulation of PD-1 by tumor accessory cells, such as mesenchymal stem cells (MSCs), which engulf the tumor microenvironment and restrain T-cell activation [33]. Moreover, Bland et al have recently discovered an alternative mechanism of melanoma derived-Exo, which affect the epigenetic landscape and mitochondrial respiration of cytotoxic T-cells.…”

Section: Role Of Exo In Melanoma Progressionmentioning

confidence: 99%

Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression

Mannavola

D’Oronzo

Cives

et al. 2019

IJMS

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Cutaneous melanoma shows a high metastatic potential based on its ability to overcome the immune system’s control. The mechanisms activated for these functions vary extremely and are also represented by the production of a number of extracellular vesicles including exosomes. Other vesicles showing a potential role in the melanoma progression include oncosomes and melanosomes and the majority of them mediate tumor processes including angiogenesis, immune regulation, and modifications of the micro-environment. Moreover, a number of epigenetic modifications have been described in melanoma and abundant production of altered microRNAs (mi-RNAs), non-coding RNAs, histones, and abnormal DNA methylation have been associated with different phases of melanoma progression. In addition, exosomes, miRNAs, and other molecular factors have been used as potential biomarkers reflecting disease evolution while others have been suggested to be potential druggable molecules for therapeutic application.

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“…Immune check point inhibitors target cell surface molecules such as programmed cell death-1 (PD-1) and Programmed cell death-ligand 1 and permit tumor cell killing by tumor-specific CTL. However, recent studies have shown that PD-L1 is often found on exosomes, playing key roles in spreading immunosuppression [76][77][78][79][80][81]. Chemotherapeutics are also reported to be secreted with exosomes.…”

Section: Exosomal Ejection Of Drugsmentioning

confidence: 99%

Exosome Release of Drugs: Coupling with Epithelial-Mesenchymal Transition

Eguchi¹,

Ono²,

Calderwood³

et al. 2019

Preprint

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Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

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The role of exosomal PD-L1 in tumor progression and immunotherapy

Cited by 273 publications

References 92 publications

Basis of PD1/PD-L1 Therapies

Basis of PD1/PD-L1 Therapies

Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression

Exosome Release of Drugs: Coupling with Epithelial-Mesenchymal Transition

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