Methotrexate-loaded tumour-cell-derived microvesicles can relieve biliary obstruction in patients with extrahepatic cholangiocarcinoma

Gao, Yunfeng; Zhang, Hui; Zhou, Nannan; Xu, Pingwei; Wang, Jianxiong; Gao, Yuan; Jin, Xun; Liang, Xiaoyu; Lv, Jiadi; Zhang, Yamin; Tang, Ke; Ma, Jingwei; Zhang, Huafeng; Xie, Jing; Yao, Fang; Tong, Wei‐Min; Liu, Yuying; Wang, Ximo; Huang, Bo

doi:10.1038/s41551-020-0583-0

Cited by 112 publications

(96 citation statements)

References 43 publications

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“…Given the merits of drug‐packaging human tumor cell‐derived MPs, their use to target CCA tumor cells might be a mean to kill tumor cells and relieve the obstruction. In a recent clinical trial, injection of methotrexate (MTX)‐MPs via percutaneous transhepatic biliary drainage (PTBD) to the bile duct lumen for 7‐day treatment with patients with CCA and it could be observed a change in color of the feces to yellow [100]. Despite the strong drug resistance, CCA tumor cells are consistently very sensitive to drug MPs [100].…”

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

“…In a recent clinical trial, injection of methotrexate (MTX)‐MPs via percutaneous transhepatic biliary drainage (PTBD) to the bile duct lumen for 7‐day treatment with patients with CCA and it could be observed a change in color of the feces to yellow [100]. Despite the strong drug resistance, CCA tumor cells are consistently very sensitive to drug MPs [100]. However, the problem is that CCA tumor cells are protected by dense extracellular matrix or even basement membrane, which prevents drug MPs from gaining access to tumor cells.…”

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

“…Immune cells, especially neutrophils, can release enzymes, such as MMPs and neutrophil elastase (NE) to degrade stromal components, thus, loosening the stromal structure of tissues [101]. Analysis by flow cytometry of the bile drainage revealed that a large number of neutrophils are attracted to the bile following drug‐MP treatment [100]. Elastase and MMP 8 were found to be released from these neutrophils, which degrade the matrices, thus, abrogating the stromal barriers and allowing MTX‐MPs to gain access to CCA cells [100].…”

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

“…Analysis by flow cytometry of the bile drainage revealed that a large number of neutrophils are attracted to the bile following drug‐MP treatment [100]. Elastase and MMP 8 were found to be released from these neutrophils, which degrade the matrices, thus, abrogating the stromal barriers and allowing MTX‐MPs to gain access to CCA cells [100]. However, the question is how neutrophils are recruited to the bile by MTX‐MPs perfusion.…”

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

“…However, the question is how neutrophils are recruited to the bile by MTX‐MPs perfusion. Two molecules UDPG and C5, which are able to attract neutrophils [102, 103], are found in MTX‐MPs, thus, possibly recruiting neutrophils to the bile [100]. Besides, MTX‐MPs can also induce CCA cells to undergo pyroptosis through a gasdermin E (GSDME)‐dependent pathway.…”

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

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Tumor‐derived microparticles in tumor immunology and immunotherapy

Zhang

Tang

et al. 2020

Eur J Immunol

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Microvesicles or microparticles, a type of cytoplasm membrane‐derived extracellular vesicles, can be released by cancer cells or normal cell types. Alteration of F‐actin cytoskeleton by various signals may lead to the cytoplasm membrane encapsulating cellular contents to form microparticles, which contain various messenger molecules, including enzymes, RNAs and even DNA fragments, and are released to extracellular space. The release of microparticles by tumor cells (T‐MPs) is a very common event in tumor microenvironments. As a result, T‐MPs not only influence tumor cell biology but also profoundly forge tumor immunology. Moreover, T‐MPs can act as a natural vehicle that delivers therapeutic drugs to tumor cells and immune cells, thus, remodeling tumor microenvironments and resetting antitumor immune responses, thus, conferring T‐MPs a potential role in tumor immunotherapies and tumor vaccines. In this review, we focus on the double‐edged sword role of T‐MPs in tumor immunology, specifically in TAMs and DCs, and emphasize the application of drug‐packaging T‐MPs in cancer patients. We aim to provide a new angle to understand immuno‐oncology and new strategies for cancer immunotherapy.

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Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

Section: Drug‐packaging T‐mps Remodel Tmementioning

confidence: 99%

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Tumor‐derived microparticles in tumor immunology and immunotherapy

Zhang

Tang

et al. 2020

Eur J Immunol

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Neutrophil and Nanoparticles Delivery to Tumor: Is It Going to Carry That Weight?

Vishnevskiy

Garanina

Chernysheva

et al. 2021

Adv Healthcare Materials

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The application of cell carriers for transporting nanodrugs to the tumor draws much attention as the alternative to the passive drug delivery. In this concept, the neutrophil (NΦ) is of special interest as this cell is able to uptake nanoparticles (NPs) and cross the vascular barrier in response to tumor signaling. There is a growing body of literature describing NP–NΦ interactions in vitro and in vivo that demonstrates the opportunity of using these cells to improve the efficacy of cancer therapy. However, a number of conceptual and technical issues need to be resolved for translating the technology into clinics. The current review summarizes the recent advances and challenges associated with NP–NΦ interactions, with the special focus on the complex interplay between the NP internalization pathways and the modulation of NΦ activity, and its potential consequences for nanodrug delivery.

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From Design to Clinic: Engineered Nanobiomaterials for Immune Normalization Therapy of Cancer

Saeed

Chen

et al. 2021

Advanced Materials

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is actively involved in T cell exhaustion. TIME is comprised of various stromal cells, extracellular matrix (ECM), innate and adaptive immune cells, (such as, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and dendritic cells (DCs)), abnormal blood and lymphatic vessels, acidic pH, hypoxia, and high interstitial fluid pressure, that contribute to stunting antitumor immune response. [2] Moreover, immune checkpoints and negative regulatory pathways, for example, programmed cell death receptor 1 (PD1) and its ligand (PD-L1), indoleamine 2,3-dioxygenase 1 (IDO-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and transforming growth factor β (TGF-β) are the main culprits in TIME that promote T cell exhaustion and adaptive resistance. [3] The considerable level of interplay, complicity, and crosstalk between tumor and immune cells further adds complexity to TIME. A deeper understanding of TIME, however, is urgently needed to deal with the key mechanisms underlying the ability of TIME to evade antitumor immunity.The failure of current immunotherapeutics, such as, antibodies, immune checkpoint inhibitors, cytokines, and agonists, to target the TIME because of its complex milieu leads to tumor progression and metastasis. Preclinical and clinical studies suggest that therapeutic drugs drive cascades of systemic toxicityThe tumor immune microenvironment (TIME) is comprised of a complex milieu that contributes to stunting antitumor immune responses by restricting T cells to accumulate in the vicinity of the tumor. Nanomedicinebased strategies are being proposed as a salvage effort to reinvigorate antitumor immunity. Various strategies, however, often fail to unleash the antitumor immune response because of the paucity of appropriate therapeutic targets in the complex TIME, invigorating a fervor of investigation into mechanisms underlying the TIME to resist nanomedicines. In this review article, effective nano/biomaterial-based delivery and TIME normalization approaches that promote T cell-mediated antitumor immune response will be discussed, with a focus on emerging preclinical and clinical strategies for immune normalization. Based on currently available evidence, it seems as if the ultimate success of cancer immunotherapy and nanomedicine hinges on the capacity to normalize the TIME. Here, how nanomedicines target immunosuppressive cells and signaling pathways to broaden the impact of cancer immunotherapy are explored. Acquisition of the urgently needed knowledge of nanomedicine-mediated immune normalization will guide researchers and scientists towards clinical applications of cancer immunotherapy.

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Methotrexate-loaded tumour-cell-derived microvesicles can relieve biliary obstruction in patients with extrahepatic cholangiocarcinoma

Cited by 112 publications

References 43 publications

Tumor‐derived microparticles in tumor immunology and immunotherapy

Tumor‐derived microparticles in tumor immunology and immunotherapy

Neutrophil and Nanoparticles Delivery to Tumor: Is It Going to Carry That Weight?

From Design to Clinic: Engineered Nanobiomaterials for Immune Normalization Therapy of Cancer

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