Extracellular vesicle-mediated crosstalk between melanoma and the immune system: Impact on tumor progression and therapy response

Abstract

Melanoma is a very lethal tumor type that easily spreads and colonizes regional and distant tissues. Crucial phenotypic changes that favor melanoma metastasis are interposed by the tumor microenvironment (TME), representing a complex network in which malignant cells communicate not only with each other but also with stromal and immune cells. This cell-cell communication can be mediated by extracellular vesicles (EVs), which are lipid bilayer-delimited particles capable of carrying a wide variety of bioactive compounds. Both melanoma-derived or TME-derived EVs deliver important pro-and antitumor signals implicated in various stages of tumor progression, such as proliferation, metastasis, and treatment response. In this review, we highlight the recent advances in EV-mediated crosstalk between melanoma and immune cells and other important cells of the TME, and address different aspects of this bidirectional interaction as well as how this may hinder or trigger the development and progression of melanoma. We also discuss the potential of using EVs as biomarkers and therapeutic strategies for melanoma.

uPAR+ extracellular vesicles: a robust biomarker of resistance to checkpoint inhibitor immunotherapy in metastatic melanoma patients

“…Considering that tumor-derived exosomes regulate the maturation, migration, and differentiation of immune cells, 33 their emerging role as biomarkers of response to immunotherapy, 13 34 and the tumor-promoting implications related to uPAR signaling, 35 our results lend credence to the hypothesis that higher levels of uPAR + EVs from tumor cells, DC and CD8 + T cells of non-responders may represent a condition that counters antitumor immunity systemically and implicates these as new biomarkers of innate resistance to ICIs.…”

“…12 Exosomes derived from melanoma cells have been shown to influence the cells in the TME by shifting the phenotype and function of normal immune cells from an antitumor state to a protumor state and by playing a role in modulating the response to immunotherapy. 13 Regarding response to therapy, circulating extracellular vesicle (EV)-based biomarkers derived from tumor or immune cells have demonstrated promising prospects in predicting the response to antitumor therapy with ICIs in patients with MM. [14][15][16] In patients with MM treated with ipilimumab, the higher baseline levels of T-cell-derived PD-1 + and CD28 + exosomes were associated with response to therapy in a previous study.…”

“… 12 Exosomes derived from melanoma cells have been shown to influence the cells in the TME by shifting the phenotype and function of normal immune cells from an antitumor state to a protumor state and by playing a role in modulating the response to immunotherapy. 13 …”

Therapeutic advances of miRNAs: A preclinical and clinical update

“…There are some critical studies toward miRNAs as therapeutics, such as “extracellular vesicle-related crosstalk between the two components, immune system and melanoma [27] . The role of miRNAs in cancer is an emerging field [28] .…”

Small Extracellular Vesicles in Pre-Therapy Plasma Predict Clinical Outcome in Non-Small-Cell Lung Cancer Patients

“…Small extracellular vesicles (sEV) are currently emerging as a promising source for liquid tumor biopsies, as their presence in plasma has been correlated with tumor progression and immune evasion of cancer [ 5 , 6 , 7 , 8 ]. Extracellular vesicles (EVs) are released through various mechanisms by all living cells and are present in all body fluids, including blood, urine, saliva, and ascites [ 9 ].…”