Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

Ye, Huali; Hu, Xin; Yang, Wen; Tu, Chongqi; Hornicek, Francis J.; Duan, Zhenfeng; Li, Min

doi:10.1186/s12951-022-01609-0

Cited by 21 publications

(16 citation statements)

References 111 publications

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“…In this scenario, the TME may play a relevant role in cancer progression and can influence the clinical management of these diseases [ 54 , 55 , 56 ], since it includes immune cells and stromal cells interacting with malignant cells through contact mechanisms or cytokines and subcellular structures, inducing both pro-tumor and antitumor activity. Among them, CD4+ and CD8+ T cells, together with NK cells, dendritic cells, and M1 tumor-associated macrophages (TAMs), promotes cell killing [ 57 , 58 , 59 ]. Novel approaches would aim to restore the immune function overcoming cancer suppressive effects [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas

Polerà

Mancuso

Riillo

et al. 2023

Cancers

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Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines. The T-cell-mediated pAXL×CD3ε cytotoxicity against sarcoma cells was investigated by flow cytometry, luminescence assay, and fluorescent microscopy imaging. The activation and degranulation of T cells induced by pAXL×CD3ε were evaluated by flow cytometry. The antitumor activity induced by pAXL×CD3ε in combination with trabectedin was also investigated. In vivo activity studies of pAXL×CD3ε were performed in immunocompromised mice (NSG), engrafted with human sarcoma cells and reconstituted with human peripheral blood mononuclear cells from healthy donors. Most sarcoma cells showed high expression of AXL. pAXL×CD3ε triggered T-lymphocyte activation and induced dose-dependent T-cell-mediated cytotoxicity. The combination of pAXL×CD3ε with trabectedin increased cytotoxicity. pAXL×CD3ε inhibited the in vivo growth of human sarcoma xenografts, increasing the survival of treated mice. Our data demonstrate the antitumor efficacy of pAXL×CD3ε against sarcoma cells, providing a translational framework for the clinical development of pAXL×CD3ε in the treatment of human sarcomas, aggressive and still-incurable malignancies.

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Section: Discussionmentioning

confidence: 99%

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas

Polerà

Mancuso

Riillo

et al. 2023

Cancers

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“…The suppression and communication barriers of immune cells allow immune evasion [137]. Tumour cells escape being destroyed by the immune system because the immune cells, such as neutrophils, monocytes, macrophages, dendritic cells, natural killer cells, and B and T lymphocytes, are suppressed [138].…”

Section: Immune Evasion Therapiesmentioning

confidence: 99%

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Zaidi¹,

Haque²,

Miskon³

2023

Preprint

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There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

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“…Exos are the products formed by the fusion of intraluminal vesicles derived from multi-vesicular bodies with the plasma membrane and released to the outside of the cell, which can be produced under normal or pathological conditions [ 31 ]. Multi-vesicles can fuse with lysosomes to degrade their contents, or fuse with plasma membranes to release inner membrane vesicles to the surrounding extracellular matrix, forming Exos containing a variety of bioactive substances [ 32 ]. Up to now, more than 4600 bioactive substances including proteins and nucleic acids have been found in Exos, such as dsDNA, miRNAs, major histocompatibility complex I, and heat shock protein HSC7023, which can widely participate in the regulation of various physiological and pathological processes in the body, such as antigen presentation, immune response, genetic material exchange, angiogenesis, inflammatory response, and tumor metastasis, thus playing an important role in the treatment of various diseases, such as the complex graft versus host diseases, myocardial ischemia and reperfusion injury, acute renal injury, and neurodegenerative diseases [ 33 ].…”

Section: Overview Of Evsmentioning

confidence: 99%

Application and Molecular Mechanisms of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Osteoporosis

Yang

Yuan

Cao

et al. 2022

CIMB

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Osteoporosis (OP) is a chronic bone disease characterized by decreased bone mass, destroyed bone microstructure, and increased bone fragility. Accumulative evidence shows that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes (Exos), exhibit great potential in the treatment of OP. However, the research on MSC-EVs in the treatment of OP is still in the initial stage. The potential mechanism has not been fully clarified. Therefore, by reviewing the relevant literature of MSC-EVs and OP in recent years, we summarized the latest application of bone targeted MSC-EVs in the treatment of OP and further elaborated the potential mechanism of MSC-EVs in regulating bone formation, bone resorption, bone angiogenesis, and immune regulation through internal bioactive molecules to alleviate OP, providing a theoretical basis for the related research of MSC-EVs in the treatment of OP.

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Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

Cited by 21 publications

References 111 publications

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Application and Molecular Mechanisms of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Osteoporosis

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