Table 2. Exosomal components in the biology of head and neck Cancers.

Squamous cell carcinoma
Exosomal component	Target/Tissue	Biological function
Exosomal miRNA 8485 from mesenchymal stem cells of dysplastic oral leukoplakia. 24	Dysplastic oral mucosal cell line and human tongue squamous cell carcinoma cell line.	Promotes proliferation, migration, and invasion of dysplastic oral keratinocytes.
Laminin 332 released from exosomes. 36	Over-expressed.	Associated with lymphatic metastasis.
Programmed death ligand 1 and cytotoxic T lymphocyte associated protein 4 present in the exosomes from head and neck cancer cells. 37	Induce apoptosis of T cells. Inhibit T cell proliferation.	Promotes tumor cell evasion from the immune system.
Exosomal miR 21. 40 , 43	Hypoxic oral squamous cell carcinoma cells. Down regulates Phosphate and tensin homolog Programmed cell death.	Prometastatic behaviour of tumor cells. Transfers cisplatin-resistance to non-resistant OSCC cell lines.
Exosomal miR 200-3p. 41	Inhibits the translation of CDH, ETNK1, and WRN.	Enhances the invasive potential of non-invasive tumor cells.
Exosomal CEP55. 42	ESCRT and ALIX binding region.	Cell division.
Salivary exosomal miRNA-486-5p 44	Elevated.	• Screening and diagnosis of oral cancers.
Salivary exosomal miR-24-3p. 45	Cell cycle regulatory gene PER 1	• Proliferation of Oral Squamous cell carcinoma cells
OSCC Exosomal derived miR 29a-3p. 50	Promotes M2 subtype macrophage polarization. These macrophages produce VEGF, PDGF, cytokines and MMPs.	• Promotes proliferation and invasion of Oral Squamous cell carcinoma • Promotes angiogenesis, cancer growth and metastasis.
OSCC Exosomal THBS1 51	Acts on M1 subtype of Macrophages.	• Transform macrophages into tumor associated macrophages • Regulates the migration of tumor cells.
Exosomal TGF B. 52	Reduces the expression of surface receptors NKp30 and NKG2D on natural killer lymphocytes.	• Inhibits the cellular cytotoxicity of natural killer lymphocytes.
Exosomal nuclear Kappa B – activating kinase associated protein 1 (NAP -1). 53	Interferon regulatory factor 3-dependent pathway.	• Enhanced the cytotoxicity of natural killer cells.
Exosomal EGFR. 55 , 56	Epithelial mesenchymal transition of epithelial cells.	• Inhibited by anti-EGFR cetuximab
Exosomal stress resistant protein – heat shock protein. 57		• Lymph node metastatic oral squamous cell carcinomas.
Exosomes derived from cancer associated fibroblasts. 58	Upregulation of MMP-3, MMP-9, N-Cadherin and Beta Catenin.	• Migration and invasion of CAL 27 lines.
Exosomal miR-382-5p derived from cancer-associated fibroblasts. 59	RERG/Ras/ERK pathway?	• Migration and invasion of tumor cells.

Salivary gland neoplasms
Exosomal component	Target/Tissue	Biological function
Epiregulin-enriched exosomes Derived from adenoid cystic carcinomas. 60	Down regulates the expression of E-Cadherin. Enhance the expression of vascular endothelial growth factor receptor 1 in lung endothelial cells.	• Induces epithelial-mesenchymal transition • Enhances invasion and metastasis • Generates a premetastatic niche at the site of future metastasis.
Exosomes derived from Adenoid cystic carcinoma 883 cells. 61	Down regulates the proteins of the tight junctions Claudin-1, ZO-1, and catenin.	• Promotes tumor cell migration and invasion.