Melanoma ResearchPub Date : 2025-10-01Epub Date: 2025-06-06DOI: 10.1097/CMR.0000000000001049
Michele Kreuz, Francisco Cezar A Moraes, Artur O M Lôbo, Renata P H Skov, Thais P Pincelli
{"title":"Updated meta-analysis on the risk of melanoma associated with phosphodiesterase type 5 inhibitors.","authors":"Michele Kreuz, Francisco Cezar A Moraes, Artur O M Lôbo, Renata P H Skov, Thais P Pincelli","doi":"10.1097/CMR.0000000000001049","DOIUrl":"10.1097/CMR.0000000000001049","url":null,"abstract":"<p><p>Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction, with modest adverse effects. Since 2011, concerns have arisen about increased melanoma risk in PDE5 inhibitor users. PDE5 inhibitors affect the rat sarcoma virus oncogene-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase-extracellular signal-regulated kinase signaling cascade, which is involved in melanoma formation. This systematic review and meta-analysis investigates melanoma risk in PDE5 inhibitor users. PubMed, Cochrane, and Embase were searched to examine the relationship between PDE5 inhibitors and melanoma. A random-effects model estimated pooled odds ratios (ORs) and hazard ratios (HRs), with the I ² statistic assessing heterogeneity. RStudio v4.4.2 was used for the meta-analysis, and a P value less than 0.05 was deemed significant. Eight studies including 7 620 765 patients were analyzed, with 2 123 165 (27.86%) comprising the PDE5 inhibitor-exposed group. The meta-analysis found a relationship between PDE5 inhibitor use and increased melanoma risk [OR: 1.60, 95% confidence interval (CI): 1.13-2.27, P = 0.009, I ² = 98%] and [HR: 1.10, 95% CI: 1.03-1.17, P = 0.005, I ² = 43%]. When each PDE5 inhibitor was examined separately, increased melanoma incidence was observed, though not statistically significant. The OR for sildenafil was 1.85 (95% CI: 0.97-3.51, P = 0.059, I ² = 99%), tadalafil 1.54 (95% CI: 0.79-3.00, P = 0.203, I ² = 96%), and vardenafil 1.16 (95% CI: 0.82-1.64, P = 0.391, I ² = 89%). This study suggests PDE5 inhibitor users have a higher chance of developing potentially fatal melanoma. Patients with a history of skin cancer, a family history of melanoma, or other risk factors should avoid these medications.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"293-299"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-10-01Epub Date: 2025-07-16DOI: 10.1097/CMR.0000000000001055
Li-Ping Zhang, Zhen-Guo Zhang, Jian Guan, Li-Qun Li
{"title":"Thrombospondin 2 drives liver metastasis in skin cutaneous melanoma via regulation of angiogenesis and extracellular matrix remodeling.","authors":"Li-Ping Zhang, Zhen-Guo Zhang, Jian Guan, Li-Qun Li","doi":"10.1097/CMR.0000000000001055","DOIUrl":"10.1097/CMR.0000000000001055","url":null,"abstract":"<p><p>To explore the functional role of thrombospondin 2 (THBS2) in the metastasis of skin cutaneous melanoma (SKCM), with a focus on its regulation of angiogenesis and extracellular matrix (ECM) remodeling. THBS2 expression was assessed in normal melanocytes and SKCM cell lines with varying metastatic potential. Functional analyses were conducted after THBS2 knockdown in A375 cells and overexpression in G-361 cells. Effects on migration, invasion, endothelial tube formation, and angiogenesis- and ECM-related factors were evaluated. Tumor IMmune Estimation Resource database was used for correlation analyses in SKCM samples. A liver metastasis model was established by intrasplenic injection of B16-F10 cells into Thbs2 knockout and wild-type mice, followed by quantification of hepatic metastases and molecular analysis of peritumoral liver tissue. THBS2 was highly expressed in invasive melanoma cell lines and was positively associated with VEGFA, PECAM1, and MMPs in both databases and experimental models. Knockdown of THBS2 significantly suppressed VEGFA, PECAM1, FGF2, FLT1, MMP2, MMP9, and ECM components (LAMA4, COL1A1, and COL4A1) at mRNA and protein levels, inhibited melanoma cell migration and invasion, and reduced tube formation in human umbilical vein endothelial cells. Overexpression had opposite effects. In vivo , Thbs2 knockout mice exhibited significantly fewer hepatic metastases and reduced metastatic area compared with wild-type controls. Expression of Lama4, Pecam1, Vegfa, Mmp2, and Mmp9 was markedly lower in peritumoral liver tissue of knockout mice. THBS2 promotes SKCM metastasis by enhancing angiogenesis and ECM remodeling. Targeting THBS2 may represent a promising strategy for inhibiting melanoma progression and distant organ colonization.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"306-316"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-10-01Epub Date: 2025-07-17DOI: 10.1097/CMR.0000000000001056
Cosimo Di Raimondo, Angela Fico, Mariagrazia Cicala, Raffaele Dante Caposiena Caro, Pierpaolo Di Domenico, Flavia Lozzi, Claudia Paganini, Piero Rossi, Cristina Rapanotti, Marco Galluzzo, Elena Campione, Leonardo Emberti Gialloreti, Luca Bianchi
{"title":"Peripheral blood inflammation indexes correlate with advanced stages in cutaneous melanoma: a single-center retrospective study.","authors":"Cosimo Di Raimondo, Angela Fico, Mariagrazia Cicala, Raffaele Dante Caposiena Caro, Pierpaolo Di Domenico, Flavia Lozzi, Claudia Paganini, Piero Rossi, Cristina Rapanotti, Marco Galluzzo, Elena Campione, Leonardo Emberti Gialloreti, Luca Bianchi","doi":"10.1097/CMR.0000000000001056","DOIUrl":"10.1097/CMR.0000000000001056","url":null,"abstract":"<p><p>Inflammation, well-known as one of the hallmarks of cancer, has been demonstrated to have a key role in the incidence and growth of different tumors. However, its role as a prognostic factor for melanoma has not yet been clarified. Our study aimed to evaluate the correlation of neutrophil to lymphocyte ratio (NLR), platelet to monocyte ratio (PMR), systemic inflammation index (SII), and aggregate index of systemic inflammation (AISI) with clinical stages of disease, to define whether higher values of these markers correlate with a more aggressive disease. We retrospectively analyzed NLR, PMR, SII, and AISI in a total of 129 newly diagnosed melanoma patients. All values were calculated using the complete blood count data. Higher NLR was associated with advanced stages ( P < 0.001). Mean NLR among patients with early stage disease (IB and IIA) was 2.01, while the mean NLR for patients with advanced stage disease (from stage IIB to IV) was 3.22. Mean PMR among patients with early stage disease (IB and IIA) was 520, while the mean PMR for patients with advanced stage disease was 479 ( P = 0.049). Mean AISI in the early stage was 247 and 482 in advanced stages ( P < 0.001). Mean SII was 480 in the early stage and 747 in advanced stages ( P = 0.004). Our data confirmed the association between NLR and newly reported the association of PMR, AISI, and SII with high-risk and aggressive melanoma. Further investigations are required to define a meaningful prognostic system for patients with advanced melanoma. This could help classify patients with advanced stages of disease, demanding a short follow-up.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"361-365"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-10-01Epub Date: 2025-04-01DOI: 10.1097/CMR.0000000000001037
Sidsel Pedersen, Troels Holz Borch, Inge Marie Svane, Marco Donia, Eva Ellebaek
{"title":"Steroid-refractory severe immune-related mucositis following adjuvant anti-PD-1 therapy for resectable melanoma: a case report.","authors":"Sidsel Pedersen, Troels Holz Borch, Inge Marie Svane, Marco Donia, Eva Ellebaek","doi":"10.1097/CMR.0000000000001037","DOIUrl":"10.1097/CMR.0000000000001037","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and are increasingly used, also in the adjuvant and neoadjuvant settings. ICIs, however, can induce immune-related adverse events (irAEs), which range from mild to life-threatening. As the use of ICIs expands, prompt identification and management of especially severe and life-threatening irAEs are crucial. We report a case of grade 4 steroid-refractory immune-related mucositis in a 60-year-old male treated with pembrolizumab following complete resection of stage IIIC melanoma. The patient received seven courses of adjuvant pembrolizumab without adverse events until 2 weeks after the seventh dose, when he presented with acute respiratory distress, dysphagia, and dyspnea. Examination revealed significant throat swelling and mucosal edema. Despite initial treatment with high-dose steroids, the patient's condition deteriorated, and he was admitted to the ICU for intubation and close monitoring. Infliximab was administered for steroid-refractory mucositis, resulting in rapid symptom resolution and successful extubation 5 days later. This case highlights the challenges in managing severe steroid-refractory irAEs. The rapid response to infliximab suggests the benefit of early intervention with alternative immunosuppressive agents in severe irAEs. Increased awareness of rare irAEs is essential for optimizing treatment and improving outcomes for patients receiving ICIs.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"344-346"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-10-01Epub Date: 2025-05-27DOI: 10.1097/CMR.0000000000001045
Ritwick S Mynam, Nandakumar Menon, Alexander Birbrair, Vincent T Ma
{"title":"Successful use of nivolumab and relatlimab as salvage therapy for metastatic uveal melanoma.","authors":"Ritwick S Mynam, Nandakumar Menon, Alexander Birbrair, Vincent T Ma","doi":"10.1097/CMR.0000000000001045","DOIUrl":"10.1097/CMR.0000000000001045","url":null,"abstract":"<p><p>Identification of effective systemic therapies for the treatment of metastatic uveal melanoma remains an ongoing challenge. While immune checkpoint inhibitors are frequently used to treat this disease, response rates and survival outcomes remain poor. In this case report, we present two heavily pretreated patients with metastatic uveal melanoma who had robust responses to combination nivolumab (PD-1 inhibitor) with relatlimab (LAG-3 inhibitor) as salvage treatment. We highlight the ongoing research of the uveal melanoma tumor immune microenvironment and the potential role of LAG-3 inhibition as an effective treatment strategy.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"352-356"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-10-01Epub Date: 2025-07-01DOI: 10.1097/CMR.0000000000001053
Zhen Zhao, Yuqiu Yang, Yunhong Zou, Wen Zhang
{"title":"Literature case analysis of immune checkpoint inhibitors-associated lipodystrophy.","authors":"Zhen Zhao, Yuqiu Yang, Yunhong Zou, Wen Zhang","doi":"10.1097/CMR.0000000000001053","DOIUrl":"10.1097/CMR.0000000000001053","url":null,"abstract":"<p><p>The objective of this study was to investigate the clinical characteristics of lipodystrophy induced by immune checkpoint inhibitors (ICIs). Domestic and international databases were searched as of 28 February 2025 and case reports of ICI-associated lipodystrophy were collected. Relevant information including patients' basic information, ICI application, the occurrence of lipodystrophy, etc., were extracted and descriptively analyzed. A total of 11 patients were included in the analysis, including two males and nine females, age from 34 to 76 years, with an average age of 55 years. The primary diseases were mainly lung cancer, melanoma and renal cell carcinoma. The latency period from ICI initiation to lipodystrophy diagnosis ranged from 42 to 540 days. Clinical manifestations included facial fat pad depletion and subcutaneous fat loss in trunk and extremities. Treatment regimens included pembrolizumab ( n = 3), nivolumab ( n = 6), cadonilimab ( n = 1), and nivolumab/ipilimumab combination ( n = 1). Serum leptin levels were tested in seven patients, and two had serum leptin concentrations <0.5 ng/ml, the others ranged from 0.6 to 61.1 ng/ml. Eight cases had records of glycated hemoglobin testing, of which five cases had glycated hemoglobin ≥6.5%. After being diagnosed with lipodystrophy, seven patients discontinued ICIs while four continued treatment. Four patients received steroid therapy and seven cases had no relevant records. Among the 11 patients, only one patient demonstrated subcutaneous fat improvement, and seven patients' prognosis was not reported. None of the eight patients who discontinued treatment resumed immunotherapy. ICI-associated lipodystrophy presents similar clinical features to conventional lipodystrophy but shows limited reversibility with treatment cessation or steroid intervention, necessitating increased clinical awareness.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"300-305"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-09-26DOI: 10.1097/CMR.0000000000001065
Luke Davies, Vasileios Skepastianos, Chrysoula Palazi, Georgios Skepastianos
{"title":"Contralateral axillary sentinel lymph node in chest wall melanoma: first documented case and narrative review of the literature.","authors":"Luke Davies, Vasileios Skepastianos, Chrysoula Palazi, Georgios Skepastianos","doi":"10.1097/CMR.0000000000001065","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001065","url":null,"abstract":"<p><p>This case report and literature review detail and contextualise the finding of a positive sentinel node in the contralateral axilla of a 69-year-old male with cutaneous malignant melanoma of the left chest wall. Excision biopsy confirmed nodular melanoma (Breslow thickness 6.6 mm; mitotic index 11; no ulceration or microsatellites; completely excised; pT4a). Preoperative lymphoscintigraphy identified the sentinel node in the right axilla. The patient underwent wide local excision with 2-cm margins and a sentinel lymph node biopsy, which showed no spread of disease. This was followed by six cycles of adjuvant pembrolizumab with surveillance scans remaining clear. Literature review identified 22 cases of anterior chest wall melanoma (n = 4) or breast carcinoma (n = 18) with contralateral drainage (12 case reports, two case series, and eight retrospective studies). Only one previous chest wall melanoma case with contralateral drainage was identified, but details were not reported. Thus, we present the first documented case of anterior chest wall melanoma with a contralateral sentinel node, and emphasise the importance of thorough evaluation of suspicious lesions for unexpected drainage patterns.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-09-03DOI: 10.1097/CMR.0000000000001062
Pablo Cerezuela-Fuentes, Carlos Aguado de la Rosa, Guillermo Crespo, Miguel-Ángel Berciano-Guerrero, Ainara Soria, Eva Muñoz-Couselo, Rafael López Castro, Margarita Majem, Pablo Ayala de Miguel, José Luis Manzano, Lorena Bellido, M José Lecumberri, Mónica Corral Subias, José Carlos Villa Guzmán, Berta Hernández, Enrique Espinosa, Teresa Puértolas, Lourdes Gutiérrez Sanz, Javier Medina Martínez, Vicente Palomar Abril, Salvador Martín Algarra, Iván Márquez-Rodas
{"title":"Treatment outcomes in patients with advanced mucosal melanoma in Spain: results from the real-world GEM1801 study.","authors":"Pablo Cerezuela-Fuentes, Carlos Aguado de la Rosa, Guillermo Crespo, Miguel-Ángel Berciano-Guerrero, Ainara Soria, Eva Muñoz-Couselo, Rafael López Castro, Margarita Majem, Pablo Ayala de Miguel, José Luis Manzano, Lorena Bellido, M José Lecumberri, Mónica Corral Subias, José Carlos Villa Guzmán, Berta Hernández, Enrique Espinosa, Teresa Puértolas, Lourdes Gutiérrez Sanz, Javier Medina Martínez, Vicente Palomar Abril, Salvador Martín Algarra, Iván Márquez-Rodas","doi":"10.1097/CMR.0000000000001062","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001062","url":null,"abstract":"<p><p>Patients with mucosal melanoma have lower survival rates than those with cutaneous melanoma. Recent studies have reported lower mucosal melanoma survival rates with the use of immune checkpoint inhibitors (ICIs). This study analyzed ICI treatment outcomes in patients with mucosal melanoma in a real-world context. The objective response rate, progression-free survival (PFS), and overall survival (OS) after first- and second-line ICI treatments were analyzed in a population of patients with advanced mucosal melanoma included in the observational GEM1801 study in Spain. Univariate Cox regression analysis was used to identify prognostic factors. From 1126 patients included between August 2018 and January 2024, 52 (4.6%) patients with mucosal melanoma were selected, with a median age at advanced stage diagnosis of 70 years; 50% were female. Most patients had an Eastern Cooperative Oncology Group performance status of 0 (48%). Tumors were primarily located in the lower gastrointestinal tract (40%) and the nasal cavity (35%). In the metastatic setting, 32 (62%) patients received ICI. At a median follow-up of 13.7 months, patients receiving ICI had a median PFS and OS of 9.4 [95% confidence interval (CI): 6.6-17.0] and 25.9 (95% CI: 21-not reached) months, respectively, for first-line treatment, and 5.1 (95% CI: 1.9-not reached) and 21.0 (95% CI: 11.1-not reached) months for second-line treatment. The clinical benefit of ICI treatment in mucosal melanoma is in accordance with previous clinical trials but is still limited, highlighting the need for new approaches for this patient population.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2025-08-29DOI: 10.1097/CMR.0000000000001061
Joyce J Zhu, Arpan Sahoo, Joanna J Song, Veda Naga Priya Vangala, Utsav Kapoor, George Blanck
{"title":"A high range of intrinsic disorder values for tumor resident, T-cell receptor beta V-complementarity determining region 3-J amino acid sequence assemblies correlates with better melanoma outcomes.","authors":"Joyce J Zhu, Arpan Sahoo, Joanna J Song, Veda Naga Priya Vangala, Utsav Kapoor, George Blanck","doi":"10.1097/CMR.0000000000001061","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001061","url":null,"abstract":"<p><p>Metastatic melanoma is characterized by high rates of treatment resistance. While various factors have been studied for their prognostic significance, this study evaluated the potential prognostic value of the intrinsic disorder of T-cell receptor beta (TRB) polypeptides. TRB recombination sequencing reads were extracted from tumor RNA-seq files representing The Cancer Genome Atlas, Skin Cutaneous Melanoma dataset, and genomics files representing the National Institutes of Health, phs002683 dataset. Intrinsic disorder values were computed for the TRB V-complementarity determining region 3 (CDR3)-J amino acid sequences for all cases. Survival analyses assessed overall survival and disease-specific survival for case sets based on assigning cases to upper or lower 50th percentile groups, based in turn on intrinsic disorder values. For the phs002683 dataset, intrinsic disorder values were compared between cases representing resistance to immune checkpoint inhibitors (ICIs) and cases representing no observed resistance. The results indicated that the upper 50th percentile of the range of intrinsic disorder values was linked to better outcomes. This was obtained for two TRB datasets representing different RNA-seq file, recombination read extraction algorithms, and was observed for two different intrinsic disorder models. Furthermore, low minimum various long-3 and various short-long 2 values correlated with ICI treatment resistance. The findings of this study suggest that the diversity of intrinsic disorder values representing TRB V-CDR3-J assemblies may represent a novel prognostic biomarker for metastatic melanoma cases and a potential biomarker for indicating different personalized treatments.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating neutrophils, lymphocytes and eosinophils: development and validation of the NLE Index in ICI-treated metastatic melanoma.","authors":"Fatma Pinar Açar, Caner Acar, Haydar Çağatay Yüksel, Gökhan Şahin, Bilge Bayir, Irem Özdemir, Tuğba Mermer, Burçak Karaca","doi":"10.1097/CMR.0000000000001060","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001060","url":null,"abstract":"<p><p>Prognosis for metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs) remains heterogeneous. Although neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) are established markers, we hypothesized a neutrophil-to-lymphocyte-times-eosinophil (NLE) index would offer superior stratification. We analyzed 194 metastatic melanoma patients receiving ICIs, divided into training (n = 129) and validation (n = 65) cohorts. An optimal NLE cutoff categorized patients as NLE-low or NLE-high. Survival outcomes and objective response rate (ORR) were assessed using Kaplan-Meier, Cox regression, and logistic regression. Predictive accuracy of NLE, NLR, and NER was compared. Median overall survival was significantly longer in NLE-low versus NLE-high patients (training: 31.3 versus 6.9 months; P = 0.011; validation: 33.5 versus 9.1 months; P = 0.019). Median progression-free survival also improved significantly in NLE-low patients (training: 10.6 versus 3.1 months; P = 0.029; validation: 13.7 versus 3.9 months; P = 0.012). ORR was higher in NLE-low groups (training: 46.0% versus 13.2%; P < 0.001; validation: 43.6% versus 18.2%; P = 0.078). NLE demonstrated superior predictive accuracy compared with NLR and NER. The NLE index outperforms NLR and NER in predicting survival and response in metastatic melanoma patients treated with ICIs, providing a practical clinical tool.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}