Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming

Morrissey, Samantha M.; Zhang, Fan; Ding, Chuan‐Fan; Montoya-Durango, Diego E.; Hu, Xiaoling; Yang, Chenghui; Wang, Zhen; Fang, Yuan; Fox, Matthew P.; Zhang, Huang‐Ge; Guo, Haixun; Tieri, David; Kong, Maiying; Watson, Corey T.; Mitchell, Robert A.; Zhang, Xiang; McMasters, Kelly M.; Huang, Jian; Yan, Jun

doi:10.1016/j.cmet.2021.09.002

Cited by 320 publications

(212 citation statements)

References 66 publications

Supporting

Mentioning

205

Contrasting

Unclassified

Order By: Relevance

“…EVs derived from breast cancer enhance the ability of CAFs in response to different metabolic environment by activating MYC signaling pathway in stromal cells resulting in rapid tumor growth ( Yan et al, 2018 ). Moreover, EVs released from Lewis lung carcinoma can induce immunosuppressive macrophages by NF-κB-mediated metabolism reprogramming, leading to tumor metastasis ( Morrissey et al, 2021 ).…”

Section: Tumor Microenvironment and Tumor-derived Evsmentioning

confidence: 99%

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment

Bao

Huang

Chen

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are nanosized particles released by numerous kinds of cells, which are now increasingly considered as essential vehicles of cell-to-cell communication and biomarkers in disease diagnosis and treatment. They contain a variety of biomolecular components, including lipids, proteins and nucleic acids. These functional molecules can be transmitted between tumor cells and other stromal cells such as endothelial cells, fibroblasts and immune cells utilizing EVs. As a result, tumor-derived EVs can deliver molecules to remodel the tumor microenvironment, thereby influencing cancer progression. On the one hand, tumor-derived EVs reprogram functions of endothelial cells, promote cancer-associated fibroblasts transformation, induce resistance to therapy and inhibit the immune response to form a pro-tumorigenic environment. On the other hand, tumor-derived EVs stimulate the immune response to create an anti-tumoral environment. This article focuses on presenting a comprehensive and critical overview of the potential role of tumor-derived EVs-mediated communication in the tumor microenvironment.

show abstract

Section: Tumor Microenvironment and Tumor-derived Evsmentioning

confidence: 99%

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment

Bao

Huang

Chen

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…PD-L1 was found to be present in extracted plasma exosomes of NSCLC patients in vitro , in vivo, and preclinical models. Moreover, Exo-PD-L1 has been reported to inhibit the synthesis of IL-2 and IFN-γ by CD8 + T cells, and dose-dependently reduce the overall quantity of CD8 + T cells, indicating that Exo-PD-L1 promotes the apoptosis of CD8 + T cells and tumor progression via PD-1/PD-L1 interaction [ 127 , 136 ].In addition, a recent study has shown that exosomes derived from NSCLC can also promote the expression of PD-L1 on macrophages through a NF-κB dependent and glycolysis dominated metabolic reprogramming mechanism, so as to promote tumor metastasis [ 137 ].…”

Section: The Role Of Ev Pd-l1 In Tumor Immune Microenvironmentmentioning

confidence: 99%

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

et al. 2022

View full text Add to dashboard Cite

Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets.

show abstract

“…The precise interaction pro le between tumor cells and CAFs are under intensive exploration, where the extracellular vesicles (EVs) serving as crucial cargo carriers of diverse pro-tumor molecules to mediate intercellular communication have received close attention 17,18 . Tumor cell-derived EVs speci cally modify the stromal cellular phenotype and reshape the TME to form a premetastatic niche and support tumor metastasis 19 . Conversely, EVs released from CAFs are widely internalized by tumor cells and contribute to the activation of aggressive tumor biology 20 .…”

Section: Introductionmentioning

confidence: 99%

An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis

Chen

Luo

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Cancer-associated fibroblasts (CAFs) are essential etiologic actors in promoting tumor progression via extensive reciprocal interactions with cancer cells. Yet, the biological role and regulatory mechanism of CAFs phenotype underlying lymph node (LN) metastasis of bladder cancer (BCa) remain unclear. Here, we report that BCa cell-secreted extracellular vesicles (EVs) played an important role in the CAF-enriched microenvironment, which correlated with BCa lymphangiogenesis and LN metastasis. RNA sequencing identified an EV-associated long noncoding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. LINC00665 mediated EV release from BCa cells to endow fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 upregulation to form a RAB27B-HGF-c-Myc positive feedback loop, facilitating BCa lymphangiogenesis and LN metastasis. Importantly, we demonstrate that Cabozantinib significantly suppressed LINC00665-mediated BCa LN metastasis in an orthotopic xenograft model. Our study highlights a molecular mechanism by which LINC00665 induces a RAB27B-HGF-c-Myc positive feedback loop between cancer cells and fibroblasts to sustain BCa LN metastasis, and represents LINC00665 as a potential therapeutic target in BCa LN metastasis.

show abstract

Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming

Cited by 320 publications

References 66 publications

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment

Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies

An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis

Contact Info

Product

Resources

About