Lung cancer cell-derived exosomes: progress on pivotal role and its application in diagnostic and therapeutic potential

Abstract

Lung cancer is frequently detected in an advanced stage and has an unfavourable prognosis. Conventional therapies are ineffective for the treatment of metastatic lung cancer. While certain molecular targets have been identified as having a positive response, the absence of appropriate drug carriers prevents their effective utilization. Lung cancer cell-derived exosomes (LCCDEs) have gained attention for their involvement in the development of cancer, as well as their potential for use in diagnosing, treating, and predicting the outcome of lung cancer. This is due to their biological roles and their inherent ability to transport biomolecules from the donor cells. Lung cancer-associated cell-derived extracellular vesicles (LCCDEVs) have the ability to enhance cell proliferation and metastasis, influence angiogenesis, regulate immune responses against tumours during the development of lung cancer, control drug resistance in lung cancer treatment, and are increasingly recognised as a crucial element in liquid biopsy evaluations for the detection of lung cancer. Therapeutic exosomes, which possess inherent intercellular communication capabilities, are increasingly recognised as effective vehicles for targeted drug delivery in precision medicine for tumours. This is due to their exceptional biocompatibility, minimal immunogenicity, low toxicity, prolonged circulation in the bloodstream, biodegradability, and ability to traverse different biological barriers. Currently, multiple studies are being conducted to create new means of diagnosing and predicting outcomes using LCCDEs, as well as to develop techniques for utilizing exosomes as effective carriers for medication delivery. This paper provides an overview of the current state of lung cancer and the wide range of applications of LCCDEs. The encouraging findings and technologies suggest that the utilization of LCCDEs holds promise for the clinical treatment of lung cancer patients.

Keywords: diagnostic; exosome; lung cancer; lung cancer cell-derived exosomes; therapeutic potential.

Figure 1

Types of lungs cancer.

Figure 2

Exosome structure.

Figure 3

Biogenesis of exosome.

Figure 4

Methods for isolating the exosomes. The exosomes are depicted as little, ebony spheres. The procedures are delineated as several paths, namely: (1) ultracentrifugation, (2) ultrafiltration, (3) size exclusion chromatography, (4) hydrostatic filtration dialysis, (5) immunoaffinity, (6) precipitation, and (7) microfluidics.

Figure 5

Tumour-derived exosomes (TDEs) in the tumour microenvironment. Exosomes from tumour cells abundantly release exosome to send signals to neighbouring cells. Recipient cells such as surrounding cells, tumour cells, endothelial cells, and immune cells are functionally affected by tumour-derived exosomes. TDEs regulate a variety of cellular mechanisms that promote tumour growth, immune evasion, angiogenesis, and metastasis. TDEs block immune cells such as T cells, natural killer (NK) cells, dendritic cells, and macrophages, limiting the immune system’s ability to combat tumours. This immune suppression allows the tumour to elude detection and elimination. TDEs also increase the proliferation of regulatory T cells (Tregs) and B cells (Bregs), which block anti-tumour immune responses, hence boosting the tumour’s survival. TDEs also have an effect on endothelial cells via stimulating angiogenesis, which is the development of new blood vessels. This mechanism provides nutrients and oxygen to the tumour while also increasing blood vessel permeability, which promotes metastases. Lastly, TDEs contribute to metastasis by preparing distant tissues for the entrance of circulating tumour cells, which aids in the spread of cancer to other organs.

Figure 6

Release of exosomes after cigarette smoke exposure 1.

Figure 7

The function of SOCS1 and SOCS3 in normal state.

Figure 8

The concentration of SOCS1 and SOCS3 after cigarette smoke exposure.

Figure 9

Schematic representation of exosome surface functionalization via genetic and chemical modifications for targeted therapeutic delivery. Adaptation from Akbari et al. (2023) (176).

Figure 10

Mechanisms of immune suppression by tumour-derived exosomes (TDXs) in the tumour microenvironment. Adenosine can be produced from extracellular ATP by TDE-bound CD73/CD39. In the TME, adenosine is a molecule with immunosuppressive characteristics. Adenosine can directly prevent T-cell activation by attaching to its adenosine receptors (A2R, A2BR) on T-cells. Additionally, adenosine encourages macrophage differentiation toward an M2-like phenotype. By activating PGE2 receptors (EP2, EP4), TDE containing prostaglandin E2 (PGE2) can also increase dendritic cell (DC) production of CD73 and consequently adenosine. More adenosine is produced as a result of this. Furthermore, TIM-3 coupled to TDE can encourage macrophages to adopt a pro-tumoural M2-like phenotype upon phagocytosis. Galectin-9 linked to TDE can attach to TIM-3 on Th1 cells, causing the cells to undergo apoptosis. By stimulating the release of IL-6, IL-1β, and other cytokines by nasopharyngeal carcinoma cells and myeloid cells, TDE-bound galectin-9 can also encourage the transformation of myeloid cells into tumour-favorable MDSCs. Furthermore, effector T-cell migration, proliferation, and activation, including CD4+ and CD8+, can be inhibited by TDE-bound PD-L1.Adaptation and modification from Vautrot et al. (2021) (189).