**2. Structural and molecular features of TEX**

Electron microscopic (EM) evaluation suggests that the structural features of tumor-derived exosomes are comparable to that of most other exosomes [10]. Like many other cells, tumor cells release TEX, which are spherical membrane-bound vesicles that frequently have a diameter ranging from 30 to 150 nm, forming an aggregation of varying sizes. Considering that exosomes carry cell-type-specific molecules, it has been proposed that TEXs vary from normal healthy exosomes in regards to their structural, molecular, and biomechanical features [19]. TEX have lipid bilayer membrane structures that include transmembrane proteins and receptors. Numerous proteins, nucleic acids, and a diverse range of compounds can be discovered within the exosomal cavity, specific to the cancer cell type. The nucleic acid constituents have a role in intracellular transmission, chemotherapy resilience, micro-angiogenesis, tumor microenvironment alteration, immune response modulation, and tumor invasion and metastatic stimulation [16].

According to several proteomics studies, TEX contain membrane proteins, Rab family proteins, annexin, proteins associated with the Endosomal Sorting Complexes Required for Transport (ESCRT) complex like Alix TSG101, MHC molecules, heat shock proteins, and tetraspanins (CD63, etc.), all of which are endosomal pathway proteins. TEXs have also been reported to include tumor antigens such as Mart1, gp100, TRP, and Her2-neu, TGF-β, FasL, TRAIL (TNF-related apoptosis-inducing ligand), and beta-glycan [10, 19, 20]. TEX carry molecular cargo (**Table 1**) that comprises of specific lipids, MHC components, tumor-associated antigens, and other proteins derived in part from the surface of parent tumor cells [10, 15, 16, 19, 20]. These suggest that they can either activate or repress the immune system, although several studies reveal that TEXs enhance immunosuppression in the tumor microenvironment. Exosomes secreted by primary tumor cells can be transmitted to distant metastatic organs before tumor cells arrive at their final destination, according to growing data. This procedure allows for the formation of an accommodating premetastatic niche that promotes the proliferation of disseminated tumors. TEXs have immunosuppressive and immunostimulatory effects that are not limited to the tumor microenvironment [15, 16].

Ubiquitination is a feature of normal exosomal/TEX proteins that permits them to be identified by ESCRT-0, whereas deubiquitination is critical in sorting them into ILVs. Membrane transport and fusion proteins such as annexin, Rab-GTPase, and HSPs such as Hsp60, Hsp70, and Hsp90; Tetraspanins such as CD9, CD63, CD81, CD82,


*Tumor-Derived Exosome and Immune Modulation DOI: http://dx.doi.org/10.5772/intechopen.103718*

#### **Table 1.**

*Cargo of TEX with their molecular features and functions.*

CD106, Tspan8, intercellular adhesion molecules (ICAM); MVBs associated protein such as ALIX and TSG101; and certain other proteins such as integrins, cytoskeletal construction proteins like actin and myosin are content of TEX [6, 15, 20]. These proteins are critical for exosome functioning. Since tumor cells are always under stressful conditions such as hypoxia, acidosis, nutrient shortage, etc., Hsp90 expression is high in numerous cancer cells. Hsp90 is linked to poor tumor prognosis and tumor development in breast cancer, pancreatic cancer, and leukemia. A study suggested that certain TEX's expressed surface TGF-β and beta-glycan, which can stimulate the SMAD signaling and govern fibroblast development into myofibroblasts [19, 21].

Exosome-bound miRNAs may also aid tumor growth in a number of ways.

By decreasing the expression of E-cadherin in normal fibroblasts, miR-9 in exosomes originating from triple-negative breast cancer cells (TNBC) might increase tumor cell migration and enhance the transition of fibroblasts into cancer-associated fibroblasts. Exosomal miRNAs of mesenchymal stromal cells have also been demonstrated to be transported directly to tumor cells, promoting cancer growth and inducing treatment resistance in multiple myeloma, colorectal, and gastric cancer cells [6, 21]. lncRNA is a newly discovered regulatory RNA that can be packed into exosomes and functions as a messenger in intercellular communication to control tumor development and other related processes while also reshaping the tumor microenvironment. lncRNAs-ATB, for example, a new cancer-associated lncRNA that was anomalously exhibited in many cancers, is known for enhancing tumor progression and growth primarily by competitively anchoring miRNA to stimulate epithelialmesenchymal transition (EMT) [21].

Although prevailing data indicates that TEX may have different immunetriggering/immunosuppressive activities based on the cargo they transmit and the functional capacity of immune cells in the tumor microenvironment, reconciling these two opposing factors of exosome features has proven to be challenging. TEX can potentially manipulate a wide variety of functions in target cells simultaneously, and the consequence is determined by the content of their cargo and the target cell's potential to accept or decline the conveyed signals.
