The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Ye, Lingxiao; Zhu, Zhenfeng; Chen, Xiaochuan; Zhang, Haoran; Huang, Jiaqi; Gu, Shengxian; Zhao, Xiangfu

doi:10.3390/cells10113247

Cited by 35 publications

(25 citation statements)

References 63 publications

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“…PD-L1 is an immunosuppressive ligand associated with immune evasion in cancer [ 27 ]. Multiple studies demonstrated elevated sEV PD-L1 levels in different cancer entities, which correlated with poor patient prognosis [ 28 , 29 ]. Moreover, Theodoraki et al observed that low sEV PD-L1 content is linked to shorter disease-free survival in HNC cancer and, thus, an unfavorable prognostic factor [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Immunoregulatory Biomarkers on Plasma Small Extracellular Vesicles for Disease Progression and Early Therapeutic Response in Head and Neck Cancer

Jabłońska

Rist

Spyra

et al. 2022

Cells

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Head and Neck Cancers (HNCs) have highly immunosuppressive properties. Small extracellular vesicles (sEVs), including exosomes, nanosized mediators of intercellular communication in the blood, carry immunosuppressive proteins and effectively inhibit anti-tumor immune responses in HNCs. This study evaluates immunosuppressive markers on sEVs from 40 HNC patients at different disease stages and 3- and 6-month follow-up after surgery and/or chemoradiotherapy. As controls, sEVs from normal donors (NDs) are examined. Immunoregulatory surface markers on sEVs were detected as relative fluorescence intensity (RFI) using on-bead flow cytometry, and their expression levels were monitored in the early and late stages of HNC and during follow-up. In parallel, the sEV-mediated apoptosis of CD8+ Jurkat cells was assessed. Together with TGF-β1 and PD-L1 abundance, total sEV proteins are elevated with disease progression. In contrast, total sEV protein, including TGF-β1, PD-1 and PD-L1, decrease upon therapy response during follow-up. Overall survival analysis implies that high sEV PD-1/PD-L1 content is an unfavorable prognostic marker in HNC. Consistently, the sEV-mediated induction of apoptosis in CD8+ T cells correlates with the disease activity and therapy response. These findings indicate that a combination of immunoregulatory marker profiles should be preferred over a single marker to monitor disease progression and therapy response in HNC.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Immunoregulatory Biomarkers on Plasma Small Extracellular Vesicles for Disease Progression and Early Therapeutic Response in Head and Neck Cancer

Jabłońska

Rist

Spyra

et al. 2022

Cells

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“…Without being internalized, TEX may deliver their surface ligands to T cell surface receptors to modulate gene expression and functions of T cells [164]. Binding of programmed cell death ligand 1 (PD-L1) to its receptor, programmed cell death protein 1 (PD-1), can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors [165]. Chen et al reported that TEX released by metastatic melanomas carry PD-L1 on their surface, which suppressed the function of CD8 + T cells and facilitated tumor growth [3].…”

Section: Via Surface Ligandmentioning

confidence: 99%

Tumor-Derived Exosomes in Tumor-Induced Immune Suppression

Hao

et al. 2022

IJMS

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Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer. Tumor-derived exosomes (TEX) carry a cargo of molecules different from that of normal cell-derived exosomes. TEX functions to mediate distinct biological effects such as receptor discharge and intercellular cross-talk. The immune system defenses, which may initially restrict tumor progression, are progressively blunted by the broad array of TEX molecules that activate suppressive pathways in different immune cells. Herein, we provide a review of the latest research progress on TEX in the context of tumor-mediated immune suppression and discuss the potential as well as challenges of TEX as a target of immunotherapy.

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“…When it comes to the lymphatic level, exoPD-L1 will inhibit the production of memory T cells, favoring lymphatic tumor spread. ExoPD-L1 plasma release has also been proved to be responsible for distant immunosuppression [ 22 , 23 ].…”

Section: Soluble and Exosomal Pd-l1mentioning

confidence: 99%

“…In addition to its immunosuppressive role, the most recent evidence places exoPD-L1 as one of the mechanisms of resistance to anti-PD-L1/PD-1 therapy [ 23 ]. Preclinical studies and phase I clinical trials have shown an association between the baseline levels of exoPD-L1 and a low response rate to treatment with ICI in NSCLC, metastatic melanoma, and head and neck tumors [ 21 , 22 , 23 , 24 ].…”

Section: Soluble and Exosomal Pd-l1mentioning

confidence: 99%

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC

Oitaben

Fonseca

Villanueva

et al. 2022

Cancers

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Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.

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The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Cited by 35 publications

References 63 publications

Evaluation of Immunoregulatory Biomarkers on Plasma Small Extracellular Vesicles for Disease Progression and Early Therapeutic Response in Head and Neck Cancer

Evaluation of Immunoregulatory Biomarkers on Plasma Small Extracellular Vesicles for Disease Progression and Early Therapeutic Response in Head and Neck Cancer

Tumor-Derived Exosomes in Tumor-Induced Immune Suppression

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC

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