The Interplay between Tumour Microenvironment Components in Malignant Melanoma

Abstract

Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma's clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or "inflammasome", its association with adipose tissue products, including the release of "extracellular vesicles", and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma's particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

Keywords: extracellular vesicles; malignant melanoma; microbiota; therapy targets; tumour microenvironment.

Figure 1

Cellular and extracellular components of melanoma’s microenvironment. The tumour microenvironment (TME) contains numerous cellular and extracellular components, forming together a complex, which supports melanoma development. APCs—antigen-presenting cells; CAFs—cancer-associated fibroblasts; DCs—dendritic cells; EVs—extracellular vesicles; HMGB1- high mobility group box 1 protein; MDSCs—myeloid-derived suppressor cells; miRNAs—microRNAs; PMNs—neutrophils; TCRs—T cells receptors; Tregs—regulatory T cells; ↑—increased level; ↓—decreased level.

Figure 2

Adipocytes and melanoma cells EVs ’’dialogue’’ in tumour microenvironment. Adipocytes and melanoma cells secrete EVs, which promote tumour progression and metastasis by tumour matrix remodelling, melanogenesis inhibition, fatty acid oxidation (FAO), and metabolic reprogramming into melanoma cells, along with epithelial-mesenchymal transition (EMT) induction, lipolysis, and lipogenesis genes upregulation in fat cells. EVs—extracellular vesicles; EMT—epithelial-mesenchymal transition; FAO—fatty acid oxidation; IL-6—interleukin 6; miRNA—microRNA; MMP—matrix metalloproteinase; NK cells—natural killer cells; T-cells—T lymphocytes; TNF-β—tumour necrosis factor β; ↑—increased level; ↓—decreased level.