Systematic Review

Dendritic cell-derived extracellular vesicles as a promising immunotherapeutic strategy for cancer: A Systematic Review

Introduction

The frequency of infections and the number of fatalities have significantly decreased as a result of vaccinations. Despite these advancements in medical research, effective solutions for cancer treatment remain elusive. In 2021, the World Health Organization recorded a significant 9.3 million deaths worldwide due to neoplasms, underscoring the urgent need for innovative cancer therapies.^1,2

Complementary adjuvant chemotherapy and radiotherapy are essential components of comprehensive multidisciplinary cancer treatment strategies.^3,4 However, resistance to radiotherapy and chemotherapy can lead to treatment inefficacy or cancer recurrence, complicating patient outcomes. While chemotherapy and radiotherapy are effective, their adverse effects limit their clinical use and often discourage patients from undergoing treatment. These limitations highlight the urgent necessity to explore novel cancer therapies that exhibit high specificity and efficacy in eliminating cancerous cells while preserving the integrity of healthy cells.^5-9 The utilization of stem cells has garnered considerable attention in the field of cancer immunotherapy, primarily due to their capacity to differentiate into diverse immune cell populations.^10,11 This innovative approach shows promise in overcoming challenges associated with existing immunotherapies, such as reduced tumor-killing potency and lack of in vivo specificity. Advancements in cell-based immunotherapy can be achieved by establishing cell lines that express tumor selectivity and cytotoxic functions.^12,13 Extensive research has been dedicated to potential candidates, including dendritic cells (DCs), natural killer (NK) cells, macrophages, and T-lymphocytes, all of which hold immense promise in this field. These cells are essential in activating the immune system through chemotaxis, enhancing immune responses by triggering antibody-dependent and cytokine-dependent activation in other immune cells, and directly eliminating cancer cells through cytotoxic mechanisms.^14,15 Their contributions are vital in orchestrating an effective immune response against cancer cells.

DC and CD4 + T-cells (T-helper cells) play crucial roles in regulating immune responses. They generate molecular signals such as cytokines and chemokines to guide and stimulate other immune cells.^16,17 DCs are the most powerful antigen-presenting cells in the body, crucial for regulating immune responses and tolerance. They bridge innate and adaptive immunity by activating resting T cells. DCs express co-stimulatory molecules such as CD80 and CD86, which facilitate antigen uptake from tumors and the presentation of tumor-associated antigens (TAAs) via major histocompatibility complex (MHC) molecules.^18,19

In addition to their antigen-presenting function, DCs secrete extracellular vehicles (EVs) known as DC-derived EVs (DEVs). DEVs are involved in immune responses and hold potential applications in cancer immunotherapies.^20-22 DEVs carry TAAs and possess various molecules, including T-cell co-stimulatory molecules, antigen-presenting molecules, adhesion molecules, NK modulation molecules, and EV markers. The composition of DEVs depends on the physiological state of the DCs.²³ DEVs have a significant role in activating T cells. They can directly present antigens to CD4 + and CD8 + T cells, leading to the suppression of tumor growth. DEVs can also be taken up by other DCs, providing exogenous peptide-loaded MHC (pMHC) for presentation to T cells.²⁴ This process is relevant in organ transplantation, where recipient DCs incorporate donor DEVs to stimulate all specific T cells.²⁵ DEVs can enhance T cell responses through a process called MHC cross-dressing, where they coat DCs with pMHC-loaded EVs. Additionally, DEVs can incorporate pMHC-loaded vesicles from other cell origins, such as epithelial cells, to enhance antigen presentation to T cells.²⁶

Furthermore, DEVs can directly activate NK cells, inducing cytokine release and NK cell cytotoxicity through molecules like TNF-α. These immune responses, combined with apoptotic signaling, contribute to the removal of tumor cells 27. DEVs derived from heat-shocked-activated DCs carry BAT3, which acts as a ligand for NKp30 and mediates NK cell cytotoxicity.²⁷ Conversely, tumor cells can secrete their EVs, known as tumor-derived EVs (TDEVs), which play a role in immune evasion. TDEVs can modulate the immune response by altering the tumor microenvironment and affecting various immune cells. They carry markers associated with tumor cells and can promote pro-inflammatory or anti-inflammatory responses depending on the target cells. TDEVs express programmed death-ligand 1 (PD-L1), which inhibits the functions of CD8 + T cells and contributes to adaptive immune resistance.²⁸

Understanding the roles of these EVs provides valuable insights for the development of immunotherapies and cancer treatments. This review aims to synthesize current findings on the immunotherapeutic potential of DEVs, highlighting their mechanisms of action, therapeutic efficacy, and future directions in the context of cancer treatment.

Methods

Study design and search terms

This systematic review was conducted according to the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary aim was to assess the immunotherapeutic potential of DEVs in cancer treatment. The review involved comprehensive literature searches, study selection based on predefined criteria, risk of bias assessment, data extraction, and qualitative synthesis. Search terms included dendritic cell, extracellular vesicles, exosome, microvesicle, apoptotic body, tumor, cancer, and neoplasms.

Inclusion and exclusion criteria

Studies were included in the review if they involved DEVs used in cancer treatment, encompassing both experimental and clinical studies that reported on immunological outcomes, antitumor efficacy, or safety of DEVs. Eligible studies had to be original research articles available in English. Conversely, studies were excluded if they did not focus on cancer treatment, were reviews, editorials, or non-original research articles, lacked sufficient data on outcomes related to DEVs, or were not available in English.

Study selection

Initially, records were identified through database searches and manual searches of reference lists, with duplicates subsequently removed. In the screening stage, two independent reviewers assessed the titles and abstracts of the remaining records for relevance. During the eligibility assessment, full-text articles were evaluated to ensure they met the inclusion criteria by two independent authors. Any discrepancies between the reviewers were resolved through discussion or consultation with a third reviewer, providing a thorough and unbiased selection process.

Risk of bias assessment and data extraction

Risk of bias (RoB) assessments in the included clinical trials were conducted using the JBI critical appraisal tool for quasi-experimental studies. Data extraction was carried out independently by two reviewers using a standardized extraction form to ensure consistency and accuracy. Key data collected included study characteristics (author(s), year of publication, country, study design, and cell density), intervention details (source and type of DC, methods of DEV isolation and characterization, dosage, and administration routes), and outcomes (primary outcomes such as immune response and antitumor efficacy, and secondary outcomes like safety and side effects).

Data synthesis

Due to the heterogeneity in study designs, interventions, and outcome measures, data were synthesized qualitatively. A narrative synthesis approach was used to summarize the findings across studies, focusing on DEV’s mechanisms of action, immunotherapeutic potential, and clinical implications in cancer treatment.

Results

Results of the study selection

Nine studies were included in this review’s qualitative synthesis. These studies were selected based on their relevance to the immunotherapeutic use of DEVs in cancer treatment, providing comprehensive insights into their efficacy and potential as a novel cancer therapy. The PRISMA flow diagram illustrates the study selection process (Figure 1).

Close

Figure 1.

PRISMA flow chart for systematic review

Figure 1.

PRISMA flow chart for systematic review

After searching in (PubMed, Scopus, and Google Scholar) databases, a total of 1068 articles were obtained, and 164 duplicates were removed.

After reviewing the title & abstract screening, 60 studies remained. The final review includes nine articles of the final full-text results; the rest, which had unrelated data, were deleted.

Overview of included studies

The systematic review incorporated findings from nine studies published between 2003 and 2022, encompassing a global range of research from countries including France, China, Japan, the Netherlands, Vietnam, and Germany. Of these studies, two were clinical trials, and seven were experimental studies. The primary focus of these investigations was either the characterization of DEVs or their application in stimulating immune responses through pretreatment with immune system cells (Table 1).

Purification and identification of exosomes

The predominant method for exosome purification was ultracentrifugation, with several studies also employing immunomagnetic capture and exosome precipitation kits. Exosome identification methods varied, including flow cytometry, transmission electron microscopy (TEM), and Western blotting. TEM was particularly noted for its effectiveness in directly detecting exosomes due to their small size (30-150 nm). Flow cytometry and immunofluorescence were useful for indirect identification when exosomes were coated with specific markers such as CD81 and CD63 (Table 2).

Immunotherapeutic potential and functional analysis

DEVs have shown significant promise as an immunotherapeutic agent through various mechanisms (Table 3).

Activation of T cells: Multiple studies have demonstrated DEVs’ ability to stimulate both CD8 + cytotoxic T cells and CD4 + helper T cells, which is essential for potent antitumor responses. For example, Guan et al³² reported that umbilical cord blood-derived DEVs increased T cell proliferation and cytotoxic effects, enhancing anticancer immunity in vivo. Similarly, Hsu et al³³ found that DEVs activated CD4 + and CD8 + T cells, contributing to a robust antitumor response.

NK cell stimulation: DEVs also played a crucial role in enhancing NK cell function. Besse et al³¹ observed that DEVs increased NKp30-related NK cell functions, although they did not induce cancer-specific T cell immune responses. Viaud et al³⁷ demonstrated that human DEVs could activate NK cells through a mechanism dependent on NKG2D ligands and interleukin (IL)-15Rα, leading to increased NK cell proliferation and IFN-γ production.

Cytotoxicity against tumor cells: Than et al³⁶ showed that immune cells primed with DEVs exhibited increased cytotoxicity against A549 tumor cells, highlighting the potential of DEVs to bridge natural and antigen-specific T cell responses and contribute to tumor regression.

Regulation of inflammatory responses: Li et al³⁴ found that exosomes from bone marrow-derived DCs treated with low-intensity pulsed ultrasonography could inhibit inflammatory responses in endothelial cells by suppressing the NF-κB signaling pathway, indicating a potential for DEVs in modulating inflammation-related aspects of cancer progression.

Exosome biomarkers and functional attributes

Studies also focused on the specific biomarkers and functions of DEVs:

Complement membrane regulator proteins: Clayton et al²⁹ identified that exosomes expressed CD55 and CD59 but not CD46, which are essential for maintaining exosome viability in the extracellular space.

Antigen presentation: Sakamoto et al³⁰ showed that DEVs from IFN-induced DCs had a greater ability to present antigens to CD8 + T cells compared to those from IL-4-induced DCs.

Immune cell priming: Lindenbergh et al³⁵ noted that exosomes from LPS-activated autologous monocyte-derived DCs increased the release of specific proteins and microRNAs with immune-stimulatory capacities, enhancing peptide-specific CD8 + T cell responses.

Discussion

This systematic review comprehensively evaluated the potential of DEVs as immunotherapeutic agents for cancer treatment. The nine studies included in this review, spanning from 2003 to 2022, elucidated various aspects of DEVs’ biological functions, their mechanisms of action, and their therapeutic implications. The key findings reveal that DEVs are capable of activating both T cells and NK cells, thereby inducing potent antitumor immune responses. Additionally, the studies underscored the effectiveness of ultracentrifugation and other advanced methods for exosome purification and characterization.

The ability of DEVs to activate CD4 + and CD8 + T cells is a critical finding, as these cells are essential for a robust and sustained antitumor response. Guan et al³² and Hsu et al³³ demonstrated the enhanced proliferation and cytotoxicity of T cells when stimulated by DEVs, corroborating the potential of these vesicles in eliciting adaptive immune responses. Furthermore, the activation of NK cells, as shown by Besse et al³¹ and Viaud et al,³⁷ highlights another crucial aspect of DEVs’ functionality, emphasizing their role in innate immunity. DEVs’ dual activation of both arms of the immune system suggests a comprehensive approach to immunotherapy, which is likely to result in more effective tumor eradication.

Clinical application of cell-based therapies appears challenging but promising.³⁸ Clinical trials included in the review demonstrated the feasibility and potential efficacy of DEVs-based treatments in human patients. For instance, Viaud et al³⁷ and Besse et al³¹ conducted trials that showed enhanced NK cell functions and T cell responses, albeit with varying degrees of success in eliciting cancer-specific responses. These trials underscore the necessity for further optimization and standardization of DEVs production and administration protocols to maximize therapeutic outcomes.

Despite the promising results, several challenges remain. One significant issue is the variability in DEVs’ production and purification methods. Ultracentrifugation, although widely used, may not consistently yield high-purity exosome preparations, which can affect the reproducibility and efficacy of DEVs-based therapies. Future research should focus on refining these techniques, possibly incorporating more advanced and standardized methods such as immunomagnetic capture and exosome precipitation kits, as demonstrated by Sakamoto et al³⁰ and Li et al.³⁴

Another challenge is DEVs heterogeneity of DEVs. The source of DCs and the conditions under which they are cultured can significantly influence the composition and functional properties of DEVs. This review highlights the need for a deeper understanding of these variables to ensure DEVs’ preparations are consistently potent and effective. For example, Sakamoto et al³⁰ showed that DEVs derived from IFN-induced DCs had superior antigen-presenting capabilities compared to those from IL-4-induced cells, indicating the importance of the DC maturation state in DEVs’ efficacy.

Future studies should also explore the integration of DEVs with other immunotherapeutic strategies, such as checkpoint inhibitors and adoptive cell transfer, to enhance their antitumor effects. The combination of DEVs with these therapies could overcome some of the limitations observed in monotherapy trials, leading to more robust and sustained responses.

Conclusion

The findings from this systematic review underscore the substantial potential of DEVs as a novel immunotherapeutic strategy for cancer. DEVs’ ability to activate both T cells and NK cells positions it as a powerful agent in the fight against cancer. However, further research is necessary to address the challenges of production standardization, heterogeneity, and clinical application. With continued advancements in the field, DEVs-based therapies hold promise for becoming a cornerstone of cancer immunotherapy, offering new hope for patients with challenging malignancies.

Competing Interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical Approval

Ethical approval and informed consent were not required for this study, as these studies were based on previously published articles.

References

1. Manshouri R, Coyaud E, Kundu ST, Peng DH, Stratton SA, Alton K. ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer. Nat Commun 2019; 10(1):5125. doi: 10.1038/s41467-019-12832-z [Crossref] [ Google Scholar]
2. Safaei S, Fadaee M, Rahbar Farzam O, Yari A, Poursaei E, Aslan C. Exploring the dynamic interplay between exosomes and the immune tumor microenvironment: implications for breast cancer progression and therapeutic strategies. Breast Cancer Res 2024; 26(1):57. doi: 10.1186/s13058-024-01810-z [Crossref] [ Google Scholar]
3. van Velsen EF, Stegenga MT, van Kemenade FJ, Kam BL, van Ginhoven TM, Visser WE. Evaluation of the 2015 ATA guidelines in patients with distant metastatic differentiated thyroid cancer. J Clin Endocrinol Metab 2020; 105(3):e457-65. doi: 10.1210/clinem/dgz137 [Crossref] [ Google Scholar]
4. Jafari F, Javdansirat S, Sanaie S, Naseri A, Shamekh A, Rostamzadeh D. Osteosarcoma: a comprehensive review of management and treatment strategies. Ann Diagn Pathol 2020; 49:151654. doi: 10.1016/j.anndiagpath.2020.151654 [Crossref] [ Google Scholar]
5. Zhang QY, Wang FX, Jia KK, Kong LD. Natural product interventions for chemotherapy and radiotherapy-induced side effects. Front Pharmacol 2018; 9:1253. doi: 10.3389/fphar.2018.01253 [Crossref] [ Google Scholar]
6. Safaei S, Amini M, Najjary S, Mokhtarzadeh A, Bolandi N, Saeedi H. miR-200c increases the sensitivity of breast cancer cells to doxorubicin through downregulating MDR1 gene. Exp Mol Pathol 2022; 125:104753. doi: 10.1016/j.yexmp.2022.104753 [Crossref] [ Google Scholar]
7. Daei Sorkhabi A, ZareDini M, Fazlollahi A, Sarkesh A, Naseri A, Mousavi SE. The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. BMC Pulm Med 2023; 23(1):495. doi: 10.1186/s12890-023-02755-3 [Crossref] [ Google Scholar]
8. Tirabadi S, Nahai MR, Alizadeh N, Ahmadpour Youshanlui M, Baradaran B. Different concentrations of produced recombinant TNF-α protein caused different cellular viability in breast cancer cell lines. Int J Drug Res Clin 2024; 2(1):e18. doi: 10.34172/ijdrc.2024.e18 [Crossref] [ Google Scholar]
9. Abolhasani S, Javadi S, Hassannia H, Ghalamfarsa G, Hojjat-Farsangi M, Jadidi-Niaragh F. IGF1R and HIF-1α gene silencing inhibits cancer cell growth. Int J Drug Res Clin 2023; 1(1):e17. doi: 10.34172/ijdrc.2023.e17 [Crossref] [ Google Scholar]
10. Ren J, Zhang X, Zhang Z, Pan J, Hao Z, Li J. Apoptosis inhibition enhances induced pluripotent stem cell generation during T cell reprogramming. Biochem Biophys Res Commun 2023; 656:30-7. doi: 10.1016/j.bbrc.2023.03.024 [Crossref] [ Google Scholar]
11. Feizi H, Hosseini MS, Seyedi-Sahebari S, Karimi H, Mosaddeghi-Heris R, Sadigh-Eteghad S. A systematic review of clinical efficacy and safety of cell-based therapies in Alzheimer’s disease. Dement Neuropsychol 2024; 18:e20240147. doi: 10.1590/1980-5764-dn-2024-0147 [Crossref] [ Google Scholar]
12. Wang Y, Wang C, Liu T, Qi H, Chen S, Cai X. Discovery of tetrahydropyrazolopyrazine derivatives as potent and selective MYT1 inhibitors for the treatment of cancer. J Med Chem 2024; 67(1):420-32. doi: 10.1021/acs.jmedchem.3c01476 [Crossref] [ Google Scholar]
13. Farajzadeh M, Hosseini MS, Eshaghi F, Mohebbi S, Hojjat-Farsangi M, Jadidi-Niaragh F. Combined blockade of interleukin-6 and β-catenin inhibits breast and colon tumor growth in vitro. Int J Drug Res Clin 2024; 2(1):e19. doi: 10.34172/ijdrc.2024.e19 [Crossref] [ Google Scholar]
14. Parikh BA, Piersma SJ, Pak-Wittel MA, Yang L, Schreiber RD, Yokoyama WM. Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells. PLoS Pathog 2015; 11(12):e1005323. doi: 10.1371/journal.ppat.1005323 [Crossref] [ Google Scholar]
15. Masoumi J, Ghorbaninezhad F, Saeedi H, Safaei S, Khaze Shahgoli V, Ghaffari Jolfayi A. siRNA-mediated B7H7 knockdown in gastric cancer lysate-loaded dendritic cells amplifies expansion and cytokine secretion of autologous T cells. Biomedicines 2023; 11(12):3212. doi: 10.3390/biomedicines11123212 [Crossref] [ Google Scholar]
16. Hilligan KL, Ronchese F. Antigen presentation by dendritic cells and their instruction of CD4 + T helper cell responses. Cell Mol Immunol 2020; 17(6):587-99. doi: 10.1038/s41423-020-0465-0 [Crossref] [ Google Scholar]
17. Ghorbaninezhad F, Asadzadeh Z, Masoumi J, Mokhtarzadeh A, Kazemi T, Aghebati-Maleki L. Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: From bench to bedside. Life Sci 2022; 297:120466. doi: 10.1016/j.lfs.2022.120466 [Crossref] [ Google Scholar]
18. Qian C, Cao X. Dendritic cells in the regulation of immunity and inflammation. Semin Immunol 2018; 35:3-11. doi: 10.1016/j.smim.2017.12.002 [Crossref] [ Google Scholar]
19. Moussion C, Delamarre L. Antigen cross-presentation by dendritic cells: a critical axis in cancer immunotherapy. Semin Immunol 2024; 71:101848. doi: 10.1016/j.smim.2023.101848 [Crossref] [ Google Scholar]
20. Kowal J, Tkach M. Dendritic cell extracellular vesicles. Int Rev Cell Mol Biol 2019; 349:213-49. doi: 10.1016/bs.ircmb.2019.08.005 [Crossref] [ Google Scholar]
21. Schierer S, Ostalecki C, Zinser E, Lamprecht R, Plosnita B, Stich L. Extracellular vesicles from mature dendritic cells (DC) differentiate monocytes into immature DC. Life Sci Alliance 2018; 1(6):e201800093. doi: 10.26508/lsa.201800093 [Crossref] [ Google Scholar]
22. Li J, Li J, Peng Y, Du Y, Yang Z, Qi X. Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies. J Control Release 2023; 353:423-33. doi: 10.1016/j.jconrel.2022.11.053 [Crossref] [ Google Scholar]
23. Fernández-Delgado I, Calzada-Fraile D, Sánchez-Madrid F. Immune regulation by dendritic cell extracellular vesicles in cancer immunotherapy and vaccines. Cancers (Basel) 2020; 12(12):3558. doi: 10.3390/cancers12123558 [Crossref] [ Google Scholar]
24. Speiser DE, Chijioke O, Schaeuble K, Münz C. CD4 + T cells in cancer. Nat Cancer 2023; 4(3):317-29. doi: 10.1038/s43018-023-00521-2 [Crossref] [ Google Scholar]
25. Fortunato M, Morali K, Passeri L, Gregori S. Regulatory cell therapy in organ transplantation: achievements and open questions. Front Immunol 2021; 12:641596. doi: 10.3389/fimmu.2021.641596 [Crossref] [ Google Scholar]
26. Chatterjee F, Spranger S. MHC-dressing on dendritic cells: Boosting anti-tumor immunity via unconventional tumor antigen presentation. Semin Immunol 2023; 66:101710. doi: 10.1016/j.smim.2023.101710 [Crossref] [ Google Scholar]
27. Wei L, Xiang Z, Zou Y. The role of NKG2D and its ligands in autoimmune diseases: new targets for immunotherapy. Int J Mol Sci 2023; 24(24):17545. doi: 10.3390/ijms242417545 [Crossref] [ Google Scholar]
28. Wang S, Sun J, Dastgheyb RM, Li Z. Tumor-derived extracellular vesicles modulate innate immune responses to affect tumor progression. Front Immunol 2022; 13:1045624. doi: 10.3389/fimmu.2022.1045624 [Crossref] [ Google Scholar]
29. Clayton A, Harris CL, Court J, Mason MD, Morgan BP. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur J Immunol 2003; 33(2):522-31. doi: 10.1002/immu.200310028 [Crossref] [ Google Scholar]
30. Sakamoto T, Koya T, Togi M, Yoshida K, Kato T Jr, Ishigaki Y. Different in vitro-generated MUTZ-3-derived dendritic cell types secrete dexosomes with distinct phenotypes and antigen presentation potencies. Int J Mol Sci 2022; 23(15):8362. doi: 10.3390/ijms23158362 [Crossref] [ Google Scholar]
31. Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology 2016; 5(4):e1071008. doi: 10.1080/2162402x.2015.1071008 [Crossref] [ Google Scholar]
32. Guan S, Li Q, Liu P, Xuan X, Du Y. Umbilical cord blood-derived dendritic cells loaded with BGC823 tumor antigens and DC-derived exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumor immunity in vitro and in vivo. Cent Eur J Immunol 2014; 39(2):142-51. doi: 10.5114/ceji.2014.43713 [Crossref] [ Google Scholar]
33. Hsu DH, Paz P, Villaflor G, Rivas A, Mehta-Damani A, Angevin E. Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J Immunother 2003; 26(5):440-50. doi: 10.1097/00002371-200309000-00007 [Crossref] [ Google Scholar]
34. Li X, Li X, Lin J, Sun X, Ding Q. Exosomes derived from low-intensity pulsed ultrasound-treated dendritic cells suppress tumor necrosis factor-induced endothelial inflammation. J Ultrasound Med 2019; 38(8):2081-91. doi: 10.1002/jum.14898 [Crossref] [ Google Scholar]
35. Lindenbergh MF, Koerhuis DG, Borg EG, van ‘t Veld EM, Driedonks TA, Wubbolts R. Bystander T-cells support clonal T-cell activation by controlling the release of dendritic cell-derived immune-stimulatory extracellular vesicles. Front Immunol 2019; 10:448. doi: 10.3389/fimmu.2019.00448 [Crossref] [ Google Scholar]
36. Than UT, Le HT, Hoang DH, Nguyen XH, Pham CT, Bui KT. Induction of antitumor immunity by exosomes isolated from cryopreserved cord blood monocyte-derived dendritic cells. Int J Mol Sci 2020; 21(5):1834. doi: 10.3390/ijms21051834 [Crossref] [ Google Scholar]
37. Viaud S, Terme M, Flament C, Taieb J, André F, Novault S. Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS One 2009; 4(3):e4942. doi: 10.1371/journal.pone.0004942 [Crossref] [ Google Scholar]
38. Salehi-Pourmehr H, Nouri O, Naseri A, Roshangar L, Rahbarghazi R, Sadigh-Eteghad S. Clinical application of stem cell therapy in neurogenic bladder: a systematic review and meta-analysis. Int Urogynecol J 2022; 33(8):2081-97. doi: 10.1007/s00192-021-04986-6 [Crossref] [ Google Scholar]