Immunobiology of Uveal Melanoma: State of the Art and Therapeutic Targets

Basile, Maria Sofia; Mazzon, Emanuela; Fagone, Paolo; Longo, Antonio; Russo, Andrea; Fallico, Matteo; Bonfiglio, Vincenza; Nicoletti, Ferdinando; Avitabile, Teresio; Reibaldi, Michele

doi:10.3389/fonc.2019.01145

Cited by 39 publications

(37 citation statements)

References 135 publications

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“…While immunotherapy has noticeably improved outcomes in metastatic cutaneous melanoma, this has not been the case for metastatic UM ( 148 ). A possible reason for such a different response to immunotherapy could be related to the different biological characteristics between cutaneous and UMs, as well as their different immunogenicity ( 149 , 150 ). Ipilimumab has shown a response rate of approximately 5-10%, with an overall survival ranging from 6 to 9.7 months ( 147 ).…”

Section: Surveillance and Metastatic Disease Treatmentmentioning

confidence: 99%

Current molecular and clinical insights into uveal melanoma (Review)

et al. 2021

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Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90-95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets.

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Section: Surveillance and Metastatic Disease Treatmentmentioning

confidence: 99%

Current molecular and clinical insights into uveal melanoma (Review)

et al. 2021

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“…The eye may provide a protective environment for UM development and growth. As a consequence, UM can evade immune surveillance via multiple mechanisms, including a deficiency of co-stimulatory molecules in the presentation of antigens process (CD80 and CD86), and by producing immunosuppressive cytokines, such as IDO1 [ 190 , 193 , 194 , 195 , 196 ]. In the same context, PDL-1 has been reported in around 5.1% of metastatic UMs and 10.6% of primary samples [ 97 , 197 ].…”

Section: Uveal Melanomamentioning

confidence: 99%

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives

Chacón

Pflüger

Ángel

et al. 2020

Cancers

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Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs—not associated with classical V600E/K BRAF mutations—malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.

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“…Similar to primary uveal melanoma, infiltrating immune cells are present in uveal melanoma liver metastasis [ 138 ]. Infiltrating immune cells in MUM appear to have abundance of tumor associated macrophages and variable numbers of TILs [ 139 ].…”

Section: Tumor Specific Suppression Of Nk Cells In Uveal Melanoma mentioning

confidence: 99%

Role of Natural Killer Cells in Uveal Melanoma

Javed

Milhem

2020

Cancers

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Uveal melanoma has a high mortality rate following metastasis to the liver. Despite advances in systemic immune therapy, treatment of metastatic uveal melanoma (MUM) has failed to achieve long term durable responses. Barriers to success with immune therapy include the immune regulatory nature of uveal melanoma as well as the immune tolerant environment of the liver. To adequately harness the anti-tumor potential of the immune system, non-T cell-based approaches need to be explored. Natural Killer (NK) cells possess potent ability to target tumor cells via innate and adaptive responses. In this review, we discuss evidence that highlights the role of NK cell surveillance and targeting of uveal melanoma. We also discuss the repertoire of intra-hepatic NK cells. The human liver has a vast and diverse lymphoid population and NK cells comprise 50% of the hepatic lymphocytes. Hepatic NK cells share a common niche with uveal melanoma micro-metastasis within the liver sinusoids. It is, therefore, crucial to understand and investigate the role of intra-hepatic NK cells in the control or progression of MUM.

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Immunobiology of Uveal Melanoma: State of the Art and Therapeutic Targets

Cited by 39 publications

References 135 publications

Current molecular and clinical insights into uveal melanoma (Review)

Current molecular and clinical insights into uveal melanoma (Review)

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives

Role of Natural Killer Cells in Uveal Melanoma

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