The role of exosomal PD-L1 in tumor immunotherapy

Wang, Jing; Zeng, Hao; Zhang, Hongwei; Han, Yunwei

doi:10.1016/j.tranon.2021.101047

Cited by 38 publications

(27 citation statements)

References 78 publications

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“…Its receptor, programmed cell death protein 1 (PD-1), is an immunoinhibitory receptor preferentially expressed on the surface of immune cells, especially on activated T cells [1]. The binding of PD-L1 to PD-1 inhibits cytotoxic T cell responses, while blockade of this interaction has proven to be an effective approach for various cancers [2]. However, clinical studies have shown that only some patients can achieve complete responses and disease remission.…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

Chen

et al. 2021

Cells

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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. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

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Section: Introductionmentioning

confidence: 99%

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

Zhu

Chen

et al. 2021

Cells

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“…These TEX-bound HSP70s can bind Toll-like receptor 2 (TLR2) at the surface of MDSCs, activating the STAT-3 pathway, which results in the suppression of neighboring T lymphocytes [49][50][51][52]. Finally, it has recently been shown that TEXs contain immune checkpoint proteins, such as PD-L1, TIM-3, or CD73/CD39, which suggests a potential function in ICI resistance [53][54][55][56][57].…”

Section: Texs In Immunitymentioning

confidence: 99%

Tumor-Derived Exosomes: Hidden Players in PD-1/PD-L1 Resistance

Vautrot

Bentayeb

Causse

et al. 2021

Cancers

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Recently, immunotherapy has garnered increasing importance in cancer therapy, leading to substantial improvements in patient care and survival. By blocking the immune checkpoints—protein regulators of the immune system—immunotherapy prevents immune tolerance toward tumors and reactivates the immune system, prompting it to fight cancer cell growth and diffusion. A widespread strategy for this is the blockade of the interaction between PD-L1 and PD-1. However, while patients generally respond well to immunotherapy, a certain proportion of patients present tumors that resist these treatments. This portion can be very high in some cancers and hinders cancer curability. For this reason, current efforts are focusing on combining PD-1/PD-L1 immunotherapy with the targeting of other immune checkpoints to counter resistance and achieve better results. Exosomes, small vesicles secreted by almost any cell, including tumor cells, have proven to be key actors in this resistance. The exosomes released by tumor cells spread the immune-suppressive properties of the tumor throughout the tumor microenvironment and participate in establishing metastatic niches. In this review, we will describe immune checkpoints and immune modulators whose presence in tumor-derived exosomes (TEXs) has been established. We will focus on the most promising proteins under scrutiny for use in combination with PD-1 blockade therapy in a clinical setting, such as PD-L1, CTLA-4, TIM-3, CD73/39, LAG-3, and TIGIT. We will explore the immunosuppressive impact of these exosomal proteins on a variety of immune cells. Finally, we will discuss how they can change the game in immunotherapy and guide therapeutic decisions, as well as the current limits of this approach. Depending on the viewpoint, these exosomal proteins may either provide key missing information on tumor growth and resistance mechanisms or they may be the next big challenge to overcome in improving cancer treatment.

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“…H. Kim et al, 2019). It has also been suggested that PD-L1 is expressed in EVs (Wang et al, 2021) and that Tyrosine Kinase Inhibitors (TKIs) against mutated EGFR may influence PD-L1 expression as well as the immune landscape in NSCLC (Kang et al, 2021;Liu et al, 2021). Moreover, for this investigation, we used the platform in a three-channel configuration, in order to reduce the inhomogeneous flow distribution among the capillaries that was detected when connecting 4 channels simultaneously.…”

Section: Detection Of Sevs From Malignant Pe Fluids Of Nsclc Patientsmentioning

confidence: 99%

Multiplexed electrokinetic sensor for detection and therapy monitoring of extracellular vesicles from liquid biopsies of non-small-cell lung cancer patients

Cavallaro

aringg

Sahu

et al. 2021

Preprint

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Liquid biopsies based on extracellular vesicle (EV) protein profiles represent a promising tool for treatment monitoring of tumors, including non-small-cell lung cancers (NSCLC). In this study, we present the development of an electrokinetic sensor for multiplexed surface protein profiling of EVs and analysis of clinical samples. The method detects the difference in the streaming current obtained as a result of EV binding to the inner surface of a functionalized microcapillary, thereby estimating the expression level of a surface marker. Using multiple microchannels functionalized with different antibodies in a parallel fluidic connection, we first demonstrate the capacity for simultaneous detection of multiple surface markers in small EVs (sEVs) from NSCLC cells. To investigate the prospects of liquid biopsies based on EVs, we then apply the method to profile sEVs isolated from the pleural effusion (PE) fluids of three NSCLC adenocarcinoma patients with different genomic alterations (ALK, KRAS and EGFR) and applied treatments (chemotherapy, EGFR or ALK tyrosine kinase inhibitors). These vesicles were targeted against CD9 tetraspanin, as well as EGFR and PD- L1, two markers of interest in NSCLC. The electrokinetic signals showed detection of these markers on sEVs yet highlighting distinct interpatient differences, e.g., increased EGFR levels in sEVs from a patient with EGFR mutation as compared to an ALK-mutant one. The sensors also detected differences in PD-L1 expressions, in line with those measured by complementary methods. The analysis of sEVs from a patient prior and post crizotinib treatment also revealed a significant increase in the expression of some markers, e.g. EGFR and PD-L1. The obtained results hold promise for the application of the method for tumor treatment monitoring based on sEVs from liquid biopsies.

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The role of exosomal PD-L1 in tumor immunotherapy

Cited by 38 publications

References 78 publications

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

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

Tumor-Derived Exosomes: Hidden Players in PD-1/PD-L1 Resistance

Multiplexed electrokinetic sensor for detection and therapy monitoring of extracellular vesicles from liquid biopsies of non-small-cell lung cancer patients

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