Objective To analyze the clinical characteristics and prognostic factors of patients with malignant melanoma liver metastasis. Methods The clinical data of patients with melanoma liver metastasis before first-line systemic therapy were retrospectively collected. Kaplan–Meier survival analysis was conducted to evaluate the association of clinical characteristics with overall survival (OS) and progression-free survival (PFS). Prognostic factors associated with PFS and OS were determined through Cox regression analysis. Results A total of 80 patients were included in this study. Six of these patients did not receive systemic or local antitumor therapy after the diagnosis of liver metastasis. Their median survival time after the diagnosis of liver metastasis was 2.3 months. The median OS of the remaining 74 patients was 12.83 months. Cox regression analysis determined that in the patients receiving systemic or local antitumor therapy, age and local treatment were independent prognostic factors for OS; gender and serum NSE levels were independent prognostic factors for systemic PFS and intrahepatic PFS. First-line treatment including immune checkpoint inhibitors (ICIs) may have survival benefits for patients but the difference was not statistically significant (HR=0.716, P=0.255). Among gene mutations, NRAS mutations had the highest rates (11.25%) and were associated with poor prognosis. In addition, BRAF and CKIT mutations were detected in eight (10%) and four (5%) patients, respectively. Conclusion Patients who are younger and receive local treatment have a relatively better prognosis. The first-line ICI therapy may have survival benefits for patients.

Among solid tumors,melanoma brain metastasis(MBM)has the highest incidence and is the leading cause of death in advanced melanoma patients.BRAF/MEK inhibitors and immune checkpoint inhibitors are currently effective treatments for brain metastases in melanoma patients.However,due to the existing blood-brain barrier and special intracranial microenviroment,the overall survival of patients has not been significantly improved,which has become a major difficulty in current treatment.Therefore,investigating the mechanisms of brain metastasis is crucial for refining the treatment strategies and improving the prognosis and survival outcomes in advanced melanoma patients.In this paper,the research progress of MBM mechanism in recent years is summarized,in order to provide new ideas for follow-up clinical work.

Acral melanoma(AM)is a distinct and aggressive subtype of melanoma characterized by high metastatic potential and poor prognosis.The pathogenesis and therapeutic strategies for advanced AM differ significantly from those of other melanoma subtypes,yet AM has received relatively less attention.AM exhibits high heterogeneity and a low tumor mutation burden.Mutations in braf,nras,and the tert promoter occur at much lower frequencies in AM than in cutaneous melanoma,limiting the effectiveness of treatments such as recombinant B-Raf proto oncogene serine/threonine protein kinase(BRAF)inhibitors.Additionally,reduced tumor immunogenicity due to low tumor-infiltrating lymphocyte levels contributes to the limited efficacy of immune checkpoint inhibitors,including anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated protein 4 therapies.Recent discoveries of novel therapeutic targets,such as receptor tyrosine kinases and cyclin-dependent kinases,along with emerging immune checkpoints,including V-domain immunoglobulin suppressor of T cell activation,adenosine A2A receptor,T cell immunoglobulin and ITIM domain,and T cell immunoglobulin and mucin-domain containing-3,offer new prospects for improving AM patient outcomes.Many AM treatments remain in the experimental stage,with research focusing on small-molecule targeted therapies,immune checkpoint inhibitors,and tumor microenvironment modulation.Combination strategies incorporating next-genera-tion cell therapies,oncolytic virus therapies,and therapeutic vaccines are also gaining prominence.Notably,clinical trials of personalized mRNA cancer vaccines have been promising,while antibody-drug conjugate and radionuclide-conjugated therapies present additional opportunities for enhancing AM prognosis.This article summarizes the cellular immune characteristics,mutation profiles,and tumor microenvironment of AM,as well as the current therapeutic strategies and advancements in the hope of expanding clinical benefits for AM patients.

Acral melanoma(AM)is a distinct and aggressive subtype of melanoma characterized by high metastatic potential and poor prognosis.The pathogenesis and therapeutic strategies for advanced AM differ significantly from those of other melanoma subtypes,yet AM has received relatively less attention.AM exhibits high heterogeneity and a low tumor mutation burden.Mutations in braf,nras,and the tert promoter occur at much lower frequencies in AM than in cutaneous melanoma,limiting the effectiveness of treatments such as recombinant B-Raf proto oncogene serine/threonine protein kinase(BRAF)inhibitors.Additionally,reduced tumor immunogenicity due to low tumor-infiltrating lymphocyte levels contributes to the limited efficacy of immune checkpoint inhibitors,including anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated protein 4 therapies.Recent discoveries of novel therapeutic targets,such as receptor tyrosine kinases and cyclin-dependent kinases,along with emerging immune checkpoints,including V-domain immunoglobulin suppressor of T cell activation,adenosine A2A receptor,T cell immunoglobulin and ITIM domain,and T cell immunoglobulin and mucin-domain containing-3,offer new prospects for improving AM patient outcomes.Many AM treatments remain in the experimental stage,with research focusing on small-molecule targeted therapies,immune checkpoint inhibitors,and tumor microenvironment modulation.Combination strategies incorporating next-genera-tion cell therapies,oncolytic virus therapies,and therapeutic vaccines are also gaining prominence.Notably,clinical trials of personalized mRNA cancer vaccines have been promising,while antibody-drug conjugate and radionuclide-conjugated therapies present additional opportunities for enhancing AM prognosis.This article summarizes the cellular immune characteristics,mutation profiles,and tumor microenvironment of AM,as well as the current therapeutic strategies and advancements in the hope of expanding clinical benefits for AM patients.

Among solid tumors,melanoma brain metastasis(MBM)has the highest incidence and is the leading cause of death in advanced melanoma patients.BRAF/MEK inhibitors and immune checkpoint inhibitors are currently effective treatments for brain metastases in melanoma patients.However,due to the existing blood-brain barrier and special intracranial microenviroment,the overall survival of patients has not been significantly improved,which has become a major difficulty in current treatment.Therefore,investigating the mechanisms of brain metastasis is crucial for refining the treatment strategies and improving the prognosis and survival outcomes in advanced melanoma patients.In this paper,the research progress of MBM mechanism in recent years is summarized,in order to provide new ideas for follow-up clinical work.

Cutaneous melanoma is a malignant skin cancer with a poor prognosis.However,re-cent advances in immune checkpoint blockade and targeted therapy have significantly improved outcomes in advanced-stage resectable melanoma,which have made neoadjuvant therapy a viable option for melanoma patients.Currently,several relevant clinical trials on neoadjuvant therapy have achieved significant results.This paper reviews the recent advances in neoadjuvant therapy for cutaneous melanoma,focusing on the selection of neoadjuvant therapy,subsequent surgical considerations after neoadjuvant therapy,prognostic indicators,and baseline biomarkers.

Objective:To investigate the correlation between peripheral blood lymphocyte immunophenotyping,cytokine levels before and after immune and anti-angiogenesis combined therapy,and treatment efficacy as well as prognosis in patients with advanced mucosal melanoma.Methods:A total of 28 patients with advanced mucosal melanoma admitted to the Drum Tower Hospital of Nanjing University School of Medicine from April 2019 to June 2022 were included in this analysis.All patients received combined treatment of camrelizumab(PD-1 inhibitor)and apatinib(anti-angiogenic drug).Peripheral blood samples were collected before treatment and after two cycles of treatment for lymphocyte immunophenotyping and cytokine level testing.The correlation between these immune markers and treatment efficacy as well as patient prognosis was evaluated.Results:After two cycles of treatment with camrelizumab and apatinib in patients with mucosal melanoma,the proportion of PD-1 positive cytotoxic T lymphocytes(CD3+CD8+CD279+cells)in peripheral blood was significantly reduced(P<0.001),while the proportion of NK cells(CD3-CD16+CD56+cells)was significantly increased(P=0.0054).Pre-treatment peripheral blood IFN-γ levels were found to be associated with overall survival(OS)(P=0.013).Patients with low IFN-γ levels had a median OS of 329 days,while the median OS for patients with high IFN-γ levels was not reached.Higher baseline IFN-γ levels were associated with a greater benefit in progression-free survival(PFS).Conclusion:The proportion of PD-1-positive T lymphocytes,NK cells and IFN-γ levels in peripheral blood may have predictive value for the efficacy and prognosis of advanced mucosal melanoma patients undergoing immunotherapy and anti-angiogenesis combined therapy.Future large-sample studies are needed to better characterize the clinical potential of these markers.

Uveal melanoma originates from the uveal tract and has a significant tendency to liver metastasis.Once metastasis occurs,the prognosis is poor.The current treatment options for uveal melanoma are liver-directed therapies including liver partial resection,ablation,isolated hepatic perfusion and percutaneous hepatic perfusion,hepatic artery infusion chemotherapy,transcatheter arterial chemoembolization,immune embolization,and radioembolization,and systemic treatment for metastatic uveal melanoma.This review discusses the pathogenesis of liver metastasis in uveal melanoma and reviews the current treatment options for uveal melanoma.

Uveal melanoma originates from the uveal tract and has a significant tendency to liver metastasis.Once metastasis occurs,the prognosis is poor.The current treatment options for uveal melanoma are liver-directed therapies including liver partial resection,ablation,isolated hepatic perfusion and percutaneous hepatic perfusion,hepatic artery infusion chemotherapy,transcatheter arterial chemoembolization,immune embolization,and radioembolization,and systemic treatment for metastatic uveal melanoma.This review discusses the pathogenesis of liver metastasis in uveal melanoma and reviews the current treatment options for uveal melanoma.

[摘 要] 目的：探讨恶性黑色素瘤（malignant melanoma，MM）微环境分型对MM患者预后的评估价值。方法：对2010年7月至2017年5月在南京鼓楼医院手术切除的87例原发性MM组织进行二代测序，免疫组化法检测PD-1、PD-L1、CD3+ TIL、MSH2、MSH6、PMS2和MLH1的表达。随访患者的生存时间，分析不同免疫微环境分型对患者预后的影响及其基因表达特征。结果：根据PD-L1和TIL表达水平将87例MM患者的肿瘤微环境分为4个亚型：PD-L1+ TIL+型或双阳型（15/87，17.24%）、PD-L1+ TIL-型（15/87，17.24%）、PD-L1- TIL+型（20/87，22.99%）、PD-L1- TIL-型或双阴型（37/87，42.53%）。双阳型患者的中位无病生存期显著长于双阴型患者（P<0.05），此可能与双阴型患者存在更多CDK4、MCL1、MYC、AKT2、CCND1、FGF19等预后不良基因拷贝数扩增相关；双阳型患者PD-1表达显著高于双阴型患者（P<0.01），可能与PD-L1、TIL分别与PD-1呈共表达和共不表达有关。结论：根据PD-L1及TIL表达将MM 患者微环境分为4种亚型，能够区分MM患者预后，双阴型患者存在更多预后不良基因拷贝数扩增。