Abstract
Malignant melanoma still remains a cancer with very poor survival rates, although it is at the forefront of personalized medicine. Most patients show partial responses and disease progressed due to adaptative resistance mechanisms, preventing long-lasting clinical benefits to the current treatments. The response to therapies can be shaped by not only taking into account cancer cell heterogeneity and plasticity, but also by its structural context as well as the cellular component of the tumor microenvironment (TME). Here, we review the recent development in the field of immunotherapy and target-based therapy and how, in the era of tumor micro-tissue engineering, ex-vivo assays could help to enhance our melanoma biology knowledge in its complexity, translating it in the development of successful therapeutic strategies, as well as in the prediction of therapeutic benefits.
Highlights
Melanoma is a complex disease consisting of a multistep process, involving the accumulation of genetic and/or epigenetic somatic modifications and exposition to environmental factors, where melanoma cells themselves, but constant interactions occurring between tumor cells and their surroundings play a crucial role in disease dissemination, therapy resistance, and mortality
Melanoma cells are only a part of a large ecosystem where tumor microenvironment plays an active part on their evolution and on their ability to escape to drug treatment
Recently several efforts have been addressed to the development of ex-vivo models able to recapitulate the live conditions of melanoma cells in human patients, in order to gain a better understanding of the mechanisms underlying melanoma biology and therapeutic resistance
Summary
A signature associated with T cell exclusion and immune evasion has been defined by single-cell RNA sequencing (scRNAseq) of melanoma tumors; it has been demonstrated to be able to predict clinical responses to anti-PD-1 therapy [77] Another important cellular component of TME is represented by the endothelial cells, involved in angiogenesis [78,79] and vascularization, two important processes involved in cancer cell growth. These cells provide structural integrity to the newly formed vessels and, together with pericytes that ensure their coverage and maturity [80], promote the vascularization inside tumor bed. Nerves provide the tumor with neurotransmitters that enhance its growth
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