Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment

Zhou, Wenxi; Zhou, Yu; Chen, Han Y. H.; Ning, Tingting; Chen, Hongyi; Guo, Qin; Zhang, Yiwen; Liu, Peixin; Zhang, Yujie; Li, Chao; Chu, Yongchao; Sun, Tao

doi:10.1016/j.biomaterials.2020.120546

Cited by 258 publications

(156 citation statements)

References 43 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…Interference with the galectin-9/dectin axis, which has been previously implicated in the conversion of macrophages to the M2-like phenotype, is another strategy targeting the polarization of macrophages in the PDAC TME. A nanoscale delivery system composed of bone marrow mesenchymal stem cell exosomes that were electropermeabilization-loaded with galectin-9 siRNA has been evaluated [ 177 ]. Additionally, these exosomes contained oxaliplatin to induce death in tumor cells.…”

Section: Immune Characterization Of the Tme And Impact On The Ecmmentioning

confidence: 99%

“…Additionally, these exosomes contained oxaliplatin to induce death in tumor cells. After co-delivery of the siRNA and oxaliplatin into orthotopic pancreatic tumor-bearing C57BL/6J mice, the authors found significant re-polarization of TAMs into the M1-like phenotype via flow cytometry and immunofluorescence staining of tumor sections, using CD206 as a marker for M2-like macrophages and CD 16/32 for the M1-like phenotype [ 177 ]. Given the many potential benefits of nanotechnology, such as increased stability and decreased side effects [ 178 ], they are certainly worth continued exploration for application in targeting TAMs in the PDAC TME.…”

Section: Immune Characterization Of the Tme And Impact On The Ecmmentioning

confidence: 99%

See 1 more Smart Citation

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

et al. 2021

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

show abstract

Section: Immune Characterization Of the Tme And Impact On The Ecmmentioning

confidence: 99%

Section: Immune Characterization Of the Tme And Impact On The Ecmmentioning

confidence: 99%

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In a recent study from Zhou et al, exosomes derived from bone marrow mesenchymal stem cells were loaded with siRNA and oxaliplatin and were used as an experimental treatment for pancreatic cancer in a mouse model. Their results indicated an increased uptake of these agents with exosomal delivery, indicating a greater therapeutic effect as compared to free drug both in vitro and in vivo [ 119 ].…”

Section: Use Of Exosomes In Targeted Deliverymentioning

confidence: 99%

Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment

Massey

Malik

Sikander

et al. 2021

IJMS

View full text Add to dashboard Cite

Exosomes are nanoscale vesicles generated by cells for intercellular communication. Due to their composition, significant research has been conducted to transform these particles into specific delivery systems for various disease states. In this review, we discuss the common isolation and loading methods of exosomes, some of the major roles of exosomes in the tumor microenvironment, as well as discuss recent applications of exosomes as drug delivery vessels and the resulting clinical implications.

show abstract

“…Modified EVs carrying these miRNAs were capable of re-polarizing M2 macrophages back to M1 macrophages [ 122 ]. In another study, it was demonstrated that bone marrow mesenchymal cell-derived EVs loaded via electroporation with oxaliplatin and siRNA targeting galectin-9, which by binding dectin-1 on macrophages leads to the formation of TAMs, are capable of causing tumor cell apoptosis and immunogenic cell death via oxaliplatin and interestingly reprogram M2 macrophages into M1 macrophages, all the while targeting PDA tumors specifically and remaining active in circulation [ 123 ]. These studies effectively highlight the robust impact of intercellular communication via EVs in a therapeutic context and show the importance of further investigating the potential of EVs as stable, non-toxic and deeply tissue-penetrating carriers of therapies.…”

Section: Stromal Cells Evs-mediated Crosstalkmentioning

confidence: 99%

The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

Hussain

Nigri

Tomasini

2021

Cancers

View full text Add to dashboard Cite

Deciphering the interactions between tumor and stromal cells is a growing field of research to improve pancreatic cancer-associated therapies and patients’ care. Indeed, while accounting for 50 to 90% of the tumor mass, many pieces of evidence reported that beyond their structural role, the non-tumoral cells composing the intra-tumoral microenvironment influence tumor cells’ proliferation, metabolism, cell death and resistance to therapies, among others. Simultaneously, tumor cells can influence non-tumoral neighboring or distant cells in order to shape a tumor-supportive and immunosuppressive environment as well as influencing the formation of metastatic niches. Among intercellular modes of communication, extracellular vesicles can simultaneously transfer the largest variety of signals and were recently reported as key effectors of cell–cell communication in pancreatic cancer, from its development to its evolution as well as its ability to resist available treatments. This review focuses on extracellular vesicles-mediated communication between different cellular components of pancreatic tumors, from the modulation of cellular activities and abilities to their biological and physiological relevance. Taking into consideration the intra-tumoral microenvironment and its extracellular-mediated crosstalk as main drivers of pancreatic cancer development should open up new therapeutic windows.

show abstract

Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment

Cited by 258 publications

References 43 publications

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment

The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

Contact Info

Product

Resources

About