International Journal of Inflammation, Cancer and Integrative Therapy
Open Access

Exosomes; Tumor; Microenvironment; Cancer; Cells

Introduction

Due to rising cancer death rates worldwide, cancer has emerged as a serious danger to human health [1]. Through information exchange that promotes tumour cell proliferation, angiogenesis, and distant metastasis, the tumour microenvironment (TME) is crucial to the development and spread of cancer [2]. Additionally important in some disease processes is cell communication. Cancer cells do, in fact, need to communicate with one another, with normal cells, and with the immune system in order to live, grow, and spread [3]. Exosomes have received a great deal of attention due to the unique biological functions they play in cell-to-cell communication. The TME is altered as a result of communication between the tumour and exosomes, encouraging tumour growth, survival, immune-escape, and invasion [4].

Exosomes have been shown to have specific roles in tumour initiation, development, metastasis, angiogenesis, and treatment resistance, making them one of the most important TME components [3]. Exosome-related growth factors and cytokines might either stimulate or inhibit immune cells and lymphoid components of the TME, such as B and T lymphocytes, natural killer cells, and macrophages. This would lead to immunosuppression and the development of tumours [5,6]. Exosomes have also been widely recognised for their use in medication delivery [7,8]. Exosomes' ability to get around drawbacks including low bioavailability, non-targeted cytotoxicity, and poor immunogenicity of drug carriers actually makes them the optimal drug delivery vehicles [9,10]. They have been created to deliver various medications, including small molecules, nucleic acids, and proteins, for the treatment of cancer in animal models. Under addition, different cell types release exosomes both in healthy and unhealthy settings. Exosomes contain cell-specific proteins and genetic materials that can reflect the origin and physiological state of the cells that made them. These materials could be investigated as preclinical biomarkers in a variety of cancers, including lung cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer, melanoma, breast cancer, prostate cancer, ovarian cancer, glioblastoma, and nasopharyngeal carcinoma. Alternative therapeutic approaches have also been proposed as innovative cancer treatments, including the suppression of exosome synthesis and the blocking of exosome absorption to certain receptors. All in all, the extensive use shows that a number of possible therapeutic approaches that block the synthesis, release, or absorption of tumor-derived exosomes are attractive avenues for the future development of anticancer medicines [11]. Exosomes can be produced by a variety of cells, including macrophages, dendritic cells, tumour cells, mesenchymal stem cells, epithelial cells, mast cells, endothelial progenitor cells, platelets, lymphocytes, and fibroblasts, according to growing data. Exosomes produced by various cells display a variety of traits and abilities. MSCs are the most frequent source of exosomes for cancer therapy among these cells of origin. Melanoma, breast cancer, and glioma are only a few of the tumours that are employed in labs for animal model. Exosomes from milk and cancer cells are also employed in the treatment of many illnesses in animals, in addition to those formed from MSCs [12]. Exosomes can all mediate the process of tumour growth or suppression through a variety of signal pathways, regardless of where they come from.

The TME, which includes tumour cells, different stromal cells, and the milieu in which they live, is well recognised to be exceedingly diverse. Tumor cells interact with the whole tumour microenvironment throughout the growth and spread of a tumour. Exosomes are essential for the control of the TME, according to mounting data. In fact, they can change how immune cells, stromal cells (CAFs, CSCs, and MSCs), and extracellular matrix (ECM) express themselves in the TME. Exosomes primarily control the TME by altering the expression of immune cells among them. By controlling the interaction between T lymphocytes, B lymphocytes, macrophages, natural killer (NK) cells, and the TME, exosomes can further control carcinogenesis and metastasis.

One of the most crucial cells in controlling the immune system is the T cell. In the context of infection, cancer, and autoimmune disorders, they mediate important immune responses. The close relationship between exosomes and T cells has steadily drawn a lot of attention in recent years. By secreting natural cytokines and growth factors, tumorderived exosomes (TEXs) can shield T cells from cancer cells induced apoptosis, eventually triggering the immune system and preventing tumour start and dissemination. Cytotoxic T cells commonly referred to as cytotoxic T lymphocytes (CTLs), are crucial components of the adaptive immune system [13]. Cytotoxic T cells can also be produced as a result of exosomes. For instance, antigen-presenting molecules (MHC-I, heat shock protein 70), tumour antigens (MAGE-1), and adhesion molecules are found in exosomes produced from malignant gliomas (ICAM-1). These drugs may cause CD8+ T cells to develop into glioma cell-killing CTLs.

B lymphocytes play a variety of roles in tumour immunity and are mostly involved in initiative immunity mechanisms. To boost or inhibit tumour immunity, they can produce immunoglobulins (antibodies), present antigens, deliver costimulatory signals, and release cytokines. It has been established that exosomes can mediate the aforementioned pathways to control how B cells' immunological responses to malignancies are regulated.

The primary immune cells in the TME that regulate inflammation are called macrophages. They exhibit the M1 and M2 broad phenotypes. Compared to M2 macrophages, which encourage tumour development and spread, M1 macrophages can destroy tumour cells. Exosomes can affect M1 and M2 macrophage polarisation to control the TME, according to several studies [14].

Conclusion

Exosomes are becoming important therapeutic targets in a way that is strongly related to the advancement of precision medicine. But there are still a lot of issues that need to be fixed. It is yet unclear how exosomes in the TME affect distant cell interactions within the tumour microenvironment. Exosome drug loading techniques and targeted modification technology still need to be improved for clinical use; the use of exosomes as cancer biomarkers in diagnosis is technically constrained by their size, heterogeneity, and labelling; and choosing which sources of exosomes are safe and biocompatible for drug delivery systems is still an unsolved problem. Finding RNAs and proteins that are suitable for use as tumour inhibitors and cancer biomarkers is challenging, and finding clinically relevant exosomes among the numerous other populations of exosomes secreted by nearly all body cells is also challenging. This is primarily because there are not enough sensitive and quick analysis platforms available. Exosomes' affordability, quick separation, and ease of purification continue to be the key barriers to their adoption in therapeutic applications. The involvement of exosomes from various sources also requires additional research because the exosome ideas are strongly associated with origin cells and source.

Acknowledgement:

Not applicable.

Conflict of Interest:

Author declares no conflict of interest.

1. Zhao W, Shan B, He D, Cheng Y, Li B, et al. (2019) Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance. J Cancer 10: 693-702.

Indexed at, Google Scholar , Crossref

2. Ragusa M, Barbagallo C, Cirnigliaro M, Battaglia R, Brex D, et al. (2017) Asymmetric RNA Distribution among Cells and Their Secreted Exosomes: Biomedical Meaning and Considerations on Diagnostic Applications. Front Mol Biosci 4: 66-80.

Indexed at, Google Scholar , Crossref

3. Wang S, Wang J, Wei W, Ma G (2019) Exosomes: The Indispensable Messenger in Tumor Pathogenesis and the Rising Star in Antitumor Applications. Adv Biosyst 3: 08.

Indexed at, Google Scholar , Crossref

4. Darband SG, Mirza-Aghazadeh-Attari M, Kaviani M, Mihanfar A, Sadighparvar S, et al. (2018) Exosomes: Natural nanoparticles as bio shuttles for RNAi delivery. J Control Release 289: 158-170.

Indexed at, Google Scholar , Crossref

5. De Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6: 24-37.

Indexed at, Google Scholar , Crossref

6. Yang E, Wang X, Gong Z, Yu M, Wu H, et al. (2020) Exosome-mediated metabolic reprogramming: The emerging role in tumor microenvironment remodeling and its influence on cancer progression. Signal Transduct Target Ther 5: 242.

Indexed at, Google Scholar , Crossref

7. Zhao X, Wu D, Ma X, Wang J, Hou W, et al. (2020) Exosomes as drug carriers for cancer therapy and challenges regarding exosome uptake. Biomed Pharmacother 128: 1237.

Indexed at, Google Scholar , Crossref

8. Rashed MH, Bayraktar E, Helal GK, Abd-Ellah MF, Amero P, et al. (2017) Exosomes: From Garbage Bins to Promising Therapeutic Targets. Int J Mol Sci 18: 538.

Indexed at, Google Scholar , Crossref

9. Zhang YF, Shi JB, Li C (2019) Small extracellular vesicle loading systems in cancer therapy: Current status and the way forward. Cytotherapy 21: 122-136.

Indexed at, Google Scholar , Crossref

10. Srivastava A, Amreddy N, Razaq M, Towner R, Zhao YD, et al. (2018) Exosomes as Theranostics for Lung Cancer. Adv Cancer Res 139: 1-33.

Indexed at, Google Scholar , Crossref

11. Wang Y, Zhang M, Zhou F (2020) Biological functions and clinical applications of exosomal long non-coding RNAs in cancer. J Cell Mol Med 24: 56-66.

Indexed at, Google Scholar , Crossref

12. Aqil F, Munagala R, Jeyabalan J, Agrawal A, Kyakulaga AH, et al. (2019) Milk exosomes-Natural nanoparticles for siRNA delivery. Cancer Lett 449: 186-195.

Indexed at, Google Scholar , Crossref

13. Mallegol J, Van Niel G, Lebreton C, Lepelletier Y, Candalh C, et al. (2007) T84-Intestinal Epithelial Exosomes Bear MHC Class II/Peptide Complexes Potentiating Antigen Presentation by Dendritic Cells. Gastroenterology 132: 1866-1876.

Indexed at, Google Scholar , Crossref

14. Baig MS, Roy A, Rajpoot S, Liu D, Savai R, et al. (2020) Tumor-derived exosomes in the regulation of macrophage polarization. Inflamm Res 69: 435-451.

Indexed at, Google Scholar , Crossref