First description of oesophageal melanoma in a cat and palliative treatment by endoscopic argon plasma coagulation laser.

Case summary: An 11-year-old castrated male domestic shorthair cat presented with chronic regurgitation and weight loss. Despite a 2-month history of weight loss, regurgitation intensified over 4 weeks, occurring with every food intake, even on a semi-liquid diet. Physical examination revealed thinness and dehydration, and a focal oval mass was noted in the middle mediastinum on thoracic radiography. Oesophagoscopy identified a 6 cm neoformation almost completely obstructing the oesophageal lumen. Biopsies were taken and histopathology, positivity to melanoma triple cocktail and PNL-2 by immunohistochemistry led to the diagnosis of melanocytic neoplasm. Palliative debulking with argon plasma coagulation (APC) was performed, significantly improving the cat's quality of life for 2 months. The cat survived for 107 days after diagnosis. Relevance and novel information: This case report describes the first report of melanocytic neoplasia originating from the oesophageal mucosa in a cat. In cats, melanomas outside the eyes are exceedingly rare and oesophageal neoplasms are exceptionally rare in veterinary medicine, particularly melanomas. The diagnosis relied on positive immunohistochemistry markers aligning with previous research. Treatment with APC emerged as a novel, potentially palliative approach, successfully alleviating regurgitation for 3 months. This underscores APC's potential in feline oesophageal neoplasia palliative care, which deserves further investigation in a broader feline cohort to confirm its efficacy. Overall, this report provides valuable insights into the diagnosis and treatment of oesophageal melanoma in cats.

Genetic Analysis of Melanoma Types Using Japanese Genomic Database.

OBJECTIVES: The purpose of this study is to compare genetic mutations, tumor mutation burden (TMB), and the effects of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in head and neck mucosal melanoma (HNMUM) with those in skin melanoma (SKM) and ocular melanoma (OM). METHODS: Data were analyzed for 72 consecutive patients with HNMUM, including 366 with SKM and 31 with OM, registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and October 2023. Genetic alterations and TMB were determined by FoundationOne CDx next-generation sequencing. RESULTS: The top 10 mutations in HNMUM were RAD21 (47.2%), NBN (45.8%), MYC (40.3%), LYN (31.9%), NRAS (29.1%), IRF4 (23.6%), DAXX (22.2%), KIT (22.2%), NOTCH3 (20.8%), and DDR1 (19.4%), with 16.6 ± 0.8 (mean ± SEM) mutations/individual. In SKM, BRAF (p = 0.04) mutation was associated with a significantly better prognosis. The TMB values were 5.7 ± 2.1 (mean ± SEM) in HNMUM, 4.1 ± 0.2 in SKM, and 3.4 ± 0.9 in OM, with no significant differences among the three groups. The median survival time for patients with distant metastases was 803 (95% confidence interval: 539-NA) days for HNMUM, 1413 (831-2172) days for SKM, and 1138 (438-NA) days for OM. CONCLUSIONS: The top 10 mutations in HNMUM are closer to those in OM than those in SKM. There was no significant difference in TMB values or survival rates with regard to the therapeutic effect of ICIs among the diseases, which suggests that current treatment of HNMUM with ICIs is appropriate. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

A Novel Melanin-Targeted 18F-PFPN Positron Emission Tomography Imaging for Diagnosing Ocular and Orbital Melanoma.

OBJECTIVE: 18F-N-(2-(Diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) picolinamide (18F-PFPN) is a novel positron emission tomography (PET) probe designed to specifically targets melanin. This study aimed to evaluate the diagnostic feasibility of 18F-PFPN in patients with ocular or orbital melanoma. MATERIALS AND METHODS: Three patients with pathologically confirmed ocular or orbital melanoma (one male, two females; age 41-59 years) were retrospectively reviewed. Each patient underwent comprehensive 18F-PFPN and 18F-fluorodeoxyglucose (18F-FDG) PET scans. The maximum standardized uptake value (SUVmax) of the lesion and the interference caused by background tissue were compared between 18F-PFPN and 18F-FDG PET imaging. In addition, the effect of intrinsic pigments in the uvea and retina on the interpretation of the results was examined. The contralateral non-tumorous eye of each patient served as a control. RESULTS: All primary tumors (3/3) were detected using 18F-PFPN PET, while only two primary tumors were detected using 18F-FDG PET. Within each lesion, the SUVmax of 18F-PFPN was 2.6 to 8.3 times higher than that of 18F-FDG. Regarding the quality of PET imaging, the physiological uptake of 18F-FDG PET in the brain and periocular tissues limited the imaging of tumors. However, 18F-PFPN PET minimized this interference. Notably, intrinsic pigments in the uvea and retina did not cause abnormal concentrations of 18F-PFPN, as no anomalous uptake of 18F-PFPN was detected in the healthy contralateral eyes. CONCLUSION: Compared to 18F-FDG, 18F-PFPN demonstrated higher detection rates for ocular and orbital melanomas with minimal interference from surrounding tissues. This suggests that 18F-PFPN could be a promising clinical diagnostic tool for distinguishing malignant melanoma from benign pigmentation in ocular and orbital melanomas.

RBMS1 reflects a distinct microenvironment and promotes tumor progression in ocular melanoma.

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common ocular cancer among adults with a high rate of recurrence and poor prognosis. Loss of epigenetic homeostasis disturbed gene expression patterns, resulting in oncogenesis. Herein, we comprehensively analyzed the DNA methylation, transcriptome profiles, and corresponding clinical information of UM patients through multiple machine-learning algorithms, finding that a methylation-driven gene RBMS1 was correlated with poor clinical outcomes of UM patients. RNA-seq and single-cell RNA-seq analyses revealed that RBMS1 reflected diverse tumor microenvironments, where high RBMS1 expression marked an immune active TME. Furthermore, we found that tumor cells were identified to have the higher communication probability in RBMS1+ state. The functional enrichment analysis revealed that RBMS1 was associated with pigment granule and melanosome, participating in cell proliferation as well as apoptotic signaling pathway. Biological experiments were performed and demonstrated that the silencing of RBMS1 inhibited ocular melanoma proliferation and promoted apoptosis. Our study highlighted that RBMS1 reflects a distinct microenvironment and promotes tumor progression in ocular melanoma, contributing to the therapeutic customization and clinical decision-making.

Multiple neoplasms in patients with uveal melanoma: a systematic review.

PURPOSE: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients. METHODS: A PubMed search (1980-2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms. RESULTS: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies. CONCLUSION: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients.

Unusual Presentation of Unilateral Choroidal Melanoma with Bilateral Vasculitis in Young Individual: A Case Report and Review of Literature.

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

Femtosecond pulsed laser photodynamic therapy activates melanin and eradicates malignant melanoma.

Photodynamic therapy (PDT) relies on a series of photophysical and photochemical reactions leading to cell death. While effective for various cancers, PDT has been less successful in treating pigmented melanoma due to high light absorption by melanin. Here, this limitation is addressed by 2-photon excitation of the photosensitizer (2p-PDT) using ~100 fs pulses of near-infrared laser light. A critical role of melanin in enabling rather than hindering 2p-PDT is elucidated using pigmented and non-pigmented murine melanoma clonal cell lines in vitro. The photocytotoxicities were compared between a clinical photosensitizer (Visudyne) and a porphyrin dimer (Oxdime) with ~600-fold higher σ2p value. Unexpectedly, while the 1p-PDT responses are similar in both cell lines, 2p activation is much more effective in killing pigmented than non-pigmented cells, suggesting a dominant role of melanin 2p-PDT. The potential for clinical translational is demonstrated in a conjunctival melanoma model in vivo, where complete eradication of small tumors was achieved. This work elucidates the melanin contribution in multi-photon PDT enabling significant advancement of light-based treatments that have previously been considered unsuitable in pigmented tumors.

GEC-ESTRO survey of 106Ru eye applicator practice for ocular melanoma - Physicist survey.

AIM: 106Ru eye plaque brachytherapy (BT, interventional radiotherapy) is an eye-preserving treatment for uveal melanoma performed in about 100 clinics worldwide. Despite this relatively low number, there is a considerable variation in clinical practice. In 2022, the BRAPHYQS and Head & Neck and Skin GEC-ESTRO working groups conducted a survey to map the current clinical practice. The survey consisted of a physicist and a physician part. This paper describes the physicist results. However, three physician questions with overlapping interest are included here as well. MATERIALS AND METHODS: The survey questions pertained to commissioning and quality control (QC) of the plaques, treatment planning, radiobiological correction, as well as more general questions on practice improvement. The questions overlapping with the physician survey were related to dose prescription and margins. RESULTS: Sixty-five physicist responses were included. A majority of the centres do not perform an independent measurement of the absorbed dose at reference depth, percentage depth dose (PDD) and off-axis data. A lack of calibration services and suitable equipment are the main reasons. About one third of the centres indicated that they do image based treatment planning. The use of margins and dose prescription showed a large variability, despite the availability of guidelines [1]. Many respondents expressed a strong wish for improvement in a wide range of aspects of clinical practice. CONCLUSION: The physics survey showed a wide variability regarding quality control of the 106Ru sources and treatment planning practice.

A practical method of estimating medium-heterogeneity corrected dose without a Monte Carlo calculation in ocular brachytherapy using 125I COMS plaques.

PURPOSE: To provide a practical method of estimating medium-heterogeneity corrected dose without a Monte Carlo (MC) calculation in ocular brachytherapy using 125I Collaborative Ocular Melanoma Study (COMS) plaques. METHODS AND MATERIALS: Using egs_brachy, MC simulations (1) under task group-43 assumptions with fully loaded seed configurations in water (HOMO) and (2) with effects of plaque backing, insert and inter-seed interactions (HETERO) were performed for seven 125I COMS plaques (10 mm-22 mm in diameter), and homogeneous dose (DHOMO) and heterogeneous dose (DHETERO) for central-axis and off-axis points were determined. For DHOMO, 85 Gy was normalized to a depth of 5 mm. Central-axis heterogeneity correction factors (HCFs) from a depth of 0 mm (inner sclera) to 22 mm (opposite retina) were derived from a ratio of DHETERO to DHOMO. Off-axis HCFs for optic disc/macula and lens as a function of distance from optic disc/macula (DT/MT) for various basal dimensions of tumor (BD/BM) were derived from DHETERO/DHOMO. RESULTS: Central-axis HCF varied with a dose reduction of 10.3-19.8% by heterogeneity. Off-axis HCF for optic disc/macula varied significantly depending on DT/MT and BD/BM with a dose reduction of 11.3-38.3%. Off-axis HCF for lens had a dependence on MT and BM with its variation of 11.0-19.0%. A clinical example of using HCFs to estimate DHETERO was presented. CONCLUSIONS: The practical method of using depth-dependent central-axis HCF and DT/MT- and BD/BM-dependent off-axis HCF provided in this study will facilitate a heterogeneous dose estimate for 125I COMS plaques without MC calculations.

Uveal melanoma modeling in mice and zebrafish.

Despite extensive research and refined therapeutic options, the survival for metastasized uveal melanoma (UM) patients has not improved significantly. UM, a malignant tumor originating from melanocytes in the uveal tract, can be asymptomatic and small tumors may be detected only during routine ophthalmic exams; making early detection and treatment difficult. UM is the result of a number of characteristic somatic alterations which are associated with prognosis. Although UM morphology and biology have been extensively studied, there are significant gaps in our understanding of the early stages of UM tumor evolution and effective treatment to prevent metastatic disease remain elusive. A better understanding of the mechanisms that enable UM cells to thrive and successfully metastasize is crucial to improve treatment efficacy and survival rates. For more than forty years, animal models have been used to investigate the biology of UM. This has led to a number of essential mechanisms and pathways involved in UM aetiology. These models have also been used to evaluate the effectiveness of various drugs and treatment protocols. Here, we provide an overview of the molecular mechanisms and pharmacological studies using mouse and zebrafish UM models. Finally, we highlight promising therapeutics and discuss future considerations using UM models such as optimal inoculation sites, use of BAP1mut-cell lines and the rise of zebrafish models.

Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi-institutional study.

PURPOSE: Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. MATERIALS AND METHODS: We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. RESULTS: Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first-line treatment was 18%. Three of the four patients with BRAF-mutated CM responded to dabrafenib and trametinib treatment. The median progression-free survival (PFS) and overall survival (OS) of first-line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver-directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites. CONCLUSION: CM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases.

Ophthalmic applicator displacement as a method of treating large diffuse uveal melanomas.

Purpose: The presentation of results of an ophthalmic plaque displacement as a brachytherapy treatment method of large diffuse uveal melanomas. Material and methods: This was a retrospective analysis of treatment results of 9 patients with large diffuse uveal melanomas using ophthalmic plaque displacement. Patients were treated with this method in our center between 2012 and 2021 (last follow-up visit in 2023). To achieve appropriate radiation dose distribution for large tumors with a base greater than 18 mm, brachytherapy (106Ru in 7 patients and 125I in 2 patients) with applicator displacement was used as primary treatment. Median follow-up was 2.9 years, and for patients with positive primary treatment results, it was 1.7 months. Median time to local relapse was 2.3 years. Results: In 5 patients, a positive result of local treatment was obtained, out of whom, one patient underwent enucleation due to complications. In the next 4 cases, local recurrence developed. In all tumors, the use of applicator displacement method caused that planning target volume (PTV) was effectively covered with treatment isodose. Conclusions: Brachytherapy with ocular applicator displacement allows for the treatment of tumors with base measurements larger than 18 mm. The application of this method may be considered as an alternative for eye enucleation in particular cases of large diffuse tumors, such as a neoplasm of the eye with vison, or when a patient does not consent to enucleation.

Immunotherapy for ocular melanoma: a bibliometric and visualization analysis from 1991 to 2022.

Background: In recent years, new therapeutic options to overcome the mechanisms of tumor immune suppression be effective in the treatment of cutaneous melanoma. These approaches have also been applied in ocular melanoma. The aim of this study is to present the current status and research hotspots of immunotherapy for ocular melanoma from a bibliometric perspective and to explore the field of immunotherapy for malignant ocular melanoma research. Methods: In this study, the Web of Science Core Collection database (WoSCC) and Pubmed were selected to search the literature related to immunotherapy of ocular melanoma. Using VOSviewer, CiteSpace, the R package "bibliometrix," and the bibliometric online platform through the construction and visualization of bibliometric networks, the country/region, institution, journal, author, and keywords were analyzed to predict the most recent trends in research pertaining to ocular melanoma and immunotherapy. Results: A total of 401 papers and 144 reviews related to immunotherapy of ocular melanoma were included. The United States is the main driver of research in the field, ranking first in terms of the number of publications, total citations, and H-index. The UNIVERSITY OF TEXAS SYSTEM is the most active institution, contributing the most papers. Jager, Martine is the most prolific author, and Carvajal, Richard is the most frequently cited author. CANCERS is the most published journal in the field and J CLIN ONCOL is the most cited journal. In addition to ocular melanoma and immunotherapy, the most popular keywords were "uveal melanoma" and "targeted therapy". According to keyword co-occurrence and burst analysis, uveal melanoma, immunotherapy, melanoma, metastases, bap1, tebentafusp, bioinformatics, conjunctival melanoma, immune checkpoint inhibitors, ipilimumab, pembrolizumab, and other research topics appear to be at the forefront of this field's research and have the potential to remain a hot research topic in the future. Conclusion: This is the first bibliometric study in the last 30 years to comprehensively map the knowledge structure and trends in the field of research related to ocular melanoma and immunotherapy. The results comprehensively summarize and identify research frontiers for scholars studying immunotherapy associated with ocular melanoma.

Ten years' blindness of the right eye: A rare presentation of an orbital melanoma.

Benign and malignant orbital tumours develop from the orbit or invade it from the surrounding tissues. Ocular melanoma is a rare but potentially devastating malignancy arising from the melanocytes of the uveal tract, conjunctiva, or orbit. The poor overall survival depends mainly on its high metastatic rate. Signs and symptoms are variables mainly depending on the size of the tumour. Its treatment consists generally of surgery, radiotherapy or both. We report a case of a patient suffering from unilateral blindness for the last 10 years with a recent swelling of the orbit. The pathological analysis described a uveal melanoma. The patient benefitted from a total orbital exenteration with reconstruction using a temporal flap. Thereafter, the patient received adjuvant radiotherapy and immunotherapy. The patient was in complete remission. No recurrence was highlighted after 2 years of follow-up.

Characterization and Quantitation of the Tumor Microenvironment of Uveal Melanoma.

Uveal melanoma (UM) is a highly malignant tumor of the eye. Metastatic spread of UM occurs almost exclusively via blood vessels and is of tremendous interest, as half of the patients with uveal melanoma die of metastasis in the long run. The tumor microenvironment consists of all cellular and non-cellular compounds of a solid tumor, except for the tumor cells. This study aims to provide a more detailed understanding of the tumor microenvironment of UM to build the foundation for new therapeutic targets. Fluorescence immunohistochemistry was performed to examine the localization of various cell types in the tumor microenvironment in UM. Furthermore, the presence of LAG-3 and its ligands Galectine-3 and LSECtin was examined to evaluate the potential efficacy of immune checkpoint inhibitor-based therapies. The main findings are that blood vessels are mainly located in the middle of the tumor, and that immune cells are mostly found in the outer section of the tumor. LAG-3 and Galectine-3 were found to be highly represented, whereas LSECtin barely occurred in UM. Both the predominant location of tumor-associated macrophages in the outer section of the tumor and the high presence of LAG-3 and Galectine-3 in the UM serve as attainable therapeutic targets.

The evidence for Mycobacterium avium subspecies paratuberculosis (MAP) as a cause of nonsolar uveal melanoma: a narrative review.

Background and Objective: Animal microorganisms have been proposed as a cause of human cancers associated with farming, agricultural occupation or residence, and related downstream exposures. Several studies have described uveal melanoma (UvM) as a farming-associated cancer. A possible suspect is the animal microorganism Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of paratuberculosis in dairy cows. This microbe is transmitted to humans through various means, including contact with animal faeces, contaminated dust and soil, organic fertilizers, and as workers in slaughterhouses/animal processing facilities. The objective of the current manuscript was to examine the putative association between Mycobacterium avium sub-species paratuberculosis and non-solar UvM. Methods: Online data sources (PubMed, Scopus, Cochrane Library, and Google) published in English between 1980 to present were searched for key words pertaining to MAP exposure, farming-related occupations and activities, and locations with or in the vicinity of dairy cattle. Key Content and Findings: While higher than expected rates of eye cancer have been suggested among dairy farmers, with MAP being ubiquitous in their environment, the involvement of MAP in the aetiology of non-solar UvMs (which account for ~97% of UvM cases) remains uncertain. Conclusions: Alternative explanations exist and future cause-and-effect research is needed to answer this hypothesis. A precautionary approach to exposure continues to be a prudent strategy.

Oncoviruses and melanomas: A retrospective study and literature review.

The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus (HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin-fixed and paraffin-embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty-four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p > 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra-CMs.

A miRNA-based gene therapy nanodrug synergistically enhances pro-inflammatory antitumor immunity against melanoma.

MicroRNA (miRNA)-based gene therapy is a robust approach to treating human cancers. However, the low target specificity and safety issues associated with viral vectors have limited the clinical use of miRNA therapeutics. In the present study, we aimed to develop a biocompatible nanocarrier to deliver the tumor suppressor miR-30a-5p for gene therapy of ocular melanoma. The quasi-mesoporous magnetic nanospheres (MMNs) were prepared by polyelectrolytes-mediated self-assembling Fe3O4 nanocrystals; the cationic polymer capped quasi-mesoporous inner tunnels of the MMNs facilitate high miRNA loading and protect from nuclease degradation. Then, the outer layer of the MMNs was modified with a disulfide bond bridged very low molecular weight polyethyleneimine (PEI) network to form redox-responsive nanospheres (rMMNs) that enhance the miRNA payload and enable miRNA release under glutathione-dominant tumor microenvironment. The miR-30a-5p loaded rMMNs nanodrug (miR-30a-5p@rMMNs) upregulated miR-30a-5p level and inhibited malignant phenotypes of ocular melanoma by targeting the transcription factor E2F7 both in vitro and in vivo. Additionally, rMMNs act as an enhancer to increase cancer cell apoptosis by modulating M1-like macrophage polarization and activating Fenton reaction. Thus, the rMMNs is a promising miRNA carrier for gene therapy and could enhance pro-inflammatory immunity in melanoma and other cancers. STATEMENT OF SIGNIFICANCE: • miR-30a-5p@rMMNs inhibited malignant phenotypes of ocular melanoma both in vitro and in vivo. • The rMMNs promoted M1 macrophage polarization thus synergistically enhancing pro-inflammatory anti-tumor immunity against melanoma. • The rMMNs showed no obvious toxicity under the injection dose.