## 1 Introduction  
Before the late 1960s, little was known about exosomes until their first description by two investigators namely [PERSON] and [PERSON] [1,2]. Right from these early studies, they were known to be the initiators of hydroxyapatite crystals which were formed as a result of direct budding of the plasma membrane [2]. Furthermore, in the 1980s, the term, exosome biogenesis was revealed following a study conducted by [PERSON] et al. [3] who discovered that exosomes in the seminal fluid were derived from prostrate/epididymis.  
Exosomes are extracellular vesicles (EVs) that function as signaling molecules between cells. These exosomes are secreted organelles with a single membrane usually small in size with a diameter of \(\sim\)30 to 200 nm. They are well enriched in lipids, proteins, nucleic acids, and glycoconjugates. Structurally, exosomes are a series of membrane-associated, oligomeric complexes of protein with a marked molecular diversity formed by budding in endosome and plasma membranes [4]. The term EV includes exosomes, prostaglandomes, ectosomes, microcwiscles, microparticles, tolerosomes, apoptotic bodies, and nanosviscles. Currently, available technology cannot separate exosomes from the other EVs mentioned earlier. Thus, exosomes isolated from cells and used for research related activities are best regarded as EVs, as stated in the guidelines formulated by the International Society of Extracellular Vesicles (ISEV) [5]. Cell-based membrane vesicles deliver microRNA (miRNA), messenger RNA (mRNA), and proteins through intracellular organelles. Microparticles, microcwiscles (100-1000 nm), and exosomes (20-200 nm) are three examples of membrane vesicles [6]. Exosomes undergo a cycle called exosome biogenesis to ensure quality control. Once they are released, exosomes have diverse activities such as extracellular matrix remodeling and signal transmission. Intercellular vesicles play vital roles in various health and disease aspects including immunity, cancer, tissue homeostasis, and neurodegenerative diseases. Additionally, pathogens such as viruses utilize exosome biogenesis pathways viz-a-viz by establishing host permissiveness and by assembling infectious particles [7]. Exosome isolation from diverse body fluids such as plasma, cerebrospinal fluid, semen, blood, amniotic fluid, saliva, urine, epididymal and synovial fluid, breast milk, and bronchoalveolar lavage makes them an ideal model for the development of therapeutic agents against multiple diseases [8].  
Exosomes are particularly regulated indifferent organisms during stresses [9,10], and they participate in a larger communication network in which cell connects to each other by DNA shuttling, proteins, RNA, and membrane-bound factors. Exosomes derived from tumors, commonly known as Tumor-derived exosomes (TEX), affect the surrounding tumor microenvironment (TME). As a result of the deep distribution of TEX in the blood and lymph, they have a big role in remote tissue sites and in the creation of their pre-metastatic niche referred to as the tumor macroenvironment (TMaE) [11]. TEX delivers tolerogenic signals to immune cells, prevents the proliferation of immune cells, interferes with the differentiation of monocyte, and induces apoptosis in activated CD$+ T lymphocytes leading to immune suppression via paracrine effect [12]. TEX exhibit some ligands (e.g., programmed death-ligand 1 (PD-L1)) to produce beneficial endocrine signals which provide pre-metastatic TMAE, expanding far from the primary tumor [11]. Furthermore, it was shown that the expression of PD-L1 is enhanced in melanoma cells exposed to interferon-\(\gamma\) (IFN\(\gamma\)), leading to the expression of PD-L1 in circulating melanoma exosomes derived from humans (HMEX) [13].