Pigment Cell & Melanoma Research最新文献

{"title":"An in vitro nevus explant model for studying the effects of ultraviolet radiation","authors":"Rui Wang,&nbsp;Jianglong Feng,&nbsp;Wei Zhang,&nbsp;Yu Wang,&nbsp;Hongguang Lu,&nbsp;Wen Zeng","doi":"10.1111/pcmr.13173","DOIUrl":"10.1111/pcmr.13173","url":null,"abstract":"<p>Ultraviolet radiation (UVR) has been recognized as a potential trigger for the transformation of benign melanocytic nevi into melanoma. However, the mechanisms governing the formation and progression of melanocytic nevi remain poorly understood. This lack of understanding is partly due to the difficulty in isolating and culturing nevus tissues in vitro, resulting in a dearth of robust ex vivo models for nevi. Therefore, the establishment of a reliable melanocytic nevus model is imperative. Such a model is essential for elucidating nevus pathogenesis and facilitating the development of effective therapeutic interventions. Therefore, we have sought to establish an ex vivo nevus explant model to study UVR stimulation. And the structural integrity and tissue activity of the ex vivo nevi explant model was evaluated. We then observed melanogenesis and proliferation activity of the explants after UVR stimulation. There was less blister formation after Day 3 in nevi explants under our modified medium conditions. The nevi explant was able to maintain almost the same morphological structure and tissue activity as in vivo tissue within 24 h. Following UVR stimulation, we observed increased melanogenesis and proliferation activity in nevi explants. Nevi explants could serve as an ex vivo model for UVR-induced nevi stimulation research.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"762-768"},"PeriodicalIF":3.9,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BET inhibition sensitizes innate checkpoint inhibitor resistant melanoma to anti-CTLA-4 treatment","authors":"Hsin-Yi Tseng,&nbsp;Sara Alavi,&nbsp;Stuart Gallagher,&nbsp;Helen M. McGuire,&nbsp;Peter Hersey,&nbsp;Abdullah Al Emran,&nbsp;Jessamy Tiffen","doi":"10.1111/pcmr.13174","DOIUrl":"10.1111/pcmr.13174","url":null,"abstract":"<p>Approximately 50% of melanoma patients fail to respond to immune checkpoint blockade (ICB), and acquired resistance hampers long-term survival in about half of initially responding patients. Whether targeting BET reader proteins, implicated in epigenetic dysregulation, can enhance ICB response rates and durability, remains to be determined. Here we show elevated BET proteins correlate with poor survival and ICB responses in melanoma patients. The BET inhibitor IBET151, combined with anti-CTLA-4, overcame innate ICB resistance however, sequential BET inhibition failed against acquired resistance in mouse models. Combination treatment response in the innate resistance model induced changes in tumor-infiltrating immune cells, reducing myeloid-derived suppressor cells (MDSCs). CD4+ and CD8+ T cells showed decreased expression of inhibitory receptors, with reduced TIM3, LAG3, and BTLA checkpoint expression. In human PBMCs in vitro, BET inhibition reduced expression of immune checkpoints in CD4+ and CD8+ T cells, restoring effector cytokines and downregulating the transcriptional driver TOX. BET proteins in melanoma may play an oncogenic role by inducing immune suppression and driving T cell dysfunction. The study demonstrates an effective combination for innately unresponsive melanoma patients to checkpoint inhibitor immunotherapy, yet highlights BET inhibitors' limitations in an acquired resistance context.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"744-751"},"PeriodicalIF":3.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic spectrum of albinism in Mali","authors":"Modibo Diallo,&nbsp;Ousmane Sylla,&nbsp;Mohamed Kole Sidibé,&nbsp;Claudio Plaisant,&nbsp;Elina Mercier,&nbsp;Angèle Sequeira,&nbsp;Sophie Javerzat,&nbsp;Abdelaziz Hadid,&nbsp;Eulalie Lasseaux,&nbsp;Vincent Michaud,&nbsp;Benoit Arveiler","doi":"10.1111/pcmr.13175","DOIUrl":"10.1111/pcmr.13175","url":null,"abstract":"<p>Albinism is a phenotypically and genetically heterogeneous condition characterized by a variable degree of hypopigmentation and by ocular features leading to reduced visual acuity. Whereas numerous genotypic studies have been conducted throughout the world, very little is known about the genotypic spectrum of albinism in Africa and especially in sub-Saharan Western Africa. Here we report the analysis of all known albinism genes in a series a 23 patients originating from Mali. Four were diagnosed with OCA 1 (oculocutaneous albinism type 1), 17 with OCA 2, and two with OCA 4. <i>OCA2</i> variant NM_000275.3:c.819_822delinsGGTC was most frequently encountered. Four novel variants were identified (two in <i>TYR</i>, two in <i>OCA2</i>). A deep intronic variant was found to alter splicing of the <i>OCA2</i> RNA by inclusion of a pseudo exon. Of note, the <i>OCA2</i> exon 7 deletion commonly found in eastern, central, and southern Africa was absent from this series. African patients with OCA 1 and OCA 4 had only been reported twice and once, respectively, in previous publications. This study constitutes the first report of the genotypic spectrum of albinism in a western sub-Saharan country.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"752-761"},"PeriodicalIF":3.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of EGFR-TKI on epidermal melanin unit integrity: Therapeutic implications for hypopigmented skin disorders","authors":"Ping Xu,&nbsp;Lingli Yang,&nbsp;Sylvia Lai,&nbsp;Fei Yang,&nbsp;Yasutaka Kuroda,&nbsp;Huimin Zhang,&nbsp;Daisuke Tsuruta,&nbsp;Ichiro Katayama","doi":"10.1111/pcmr.13171","DOIUrl":"10.1111/pcmr.13171","url":null,"abstract":"<p>Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real-time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin-1 (ET-1) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co-culture, as evidenced by time-lapse live imaging and single-cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol-induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET-1 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR-TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"514-529"},"PeriodicalIF":4.3,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis reveals inflammatory biomarkers for skin melanoma prognosis","authors":"Zhi-Qing Zhan,&nbsp;Jia-Xin Li,&nbsp;Xin-Lei Hu","doi":"10.1111/pcmr.13172","DOIUrl":"10.1111/pcmr.13172","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"510-513"},"PeriodicalIF":4.3,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"25th International Pigment Cell Conference, Bilbao, Spain IPCC 2023","authors":"","doi":"10.1111/pcmr.13145","DOIUrl":"10.1111/pcmr.13145","url":null,"abstract":"","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"597-655"},"PeriodicalIF":3.9,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA M6A modification shaping cutaneous melanoma tumor microenvironment and predicting immunotherapy response","authors":"Yanhong Wu,&nbsp;Hongying He,&nbsp;Kairong Zheng,&nbsp;Zhenxin Qin,&nbsp;Naikun Cai,&nbsp;Shuguang Zuo,&nbsp;Xiao Zhu","doi":"10.1111/pcmr.13170","DOIUrl":"10.1111/pcmr.13170","url":null,"abstract":"<p>Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6-methyladenosine (M6A) significance in SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using SKCM samples from TCGA and GEO databases, identifying three M6A modification patterns linked to TME cell infiltration. Principal component analysis (PCA) yielded an M6A score for individual tumors, utilizing patient gene expression profiles and CNV data from TCGA. M6A modification patterns play a crucial role in SKCM development and progression, influencing tumor attributes such as inflammatory stage, subtype, TME interstitial activity, and genetic mutations. The M6A score independently predicts patient outcomes and correlates with improved response to immunotherapy, validated across anti-PD-1 and anti-PD-L1 therapy cohorts. M6A modifications significantly impact the TME landscape, with the M6A score serving as a predictive marker for immunotherapy response. Integrating M6A-related information into clinical practice could revolutionize SKCM management and treatment strategies.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"496-509"},"PeriodicalIF":4.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular heterogeneity of quiescent melanocyte stem cells revealed by single-cell RNA-sequencing","authors":"Joseph W. Palmer,&nbsp;Nilesh Kumar,&nbsp;Luye An,&nbsp;Andrew C. White,&nbsp;M. Shahid Mukhtar,&nbsp;Melissa L. Harris","doi":"10.1111/pcmr.13169","DOIUrl":"10.1111/pcmr.13169","url":null,"abstract":"<p>Melanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole-skin, single-cell RNA sequencing (scRNA-seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45− cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g., <i>Kit+</i>, <i>Cd34+/−</i>, <i>Plp1+</i>, <i>Cd274+/−</i>, <i>Thy1+</i>, <i>Cdh3+/−</i>) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogeneous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"480-495"},"PeriodicalIF":4.3,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Mercaptonicotinoyl glycine, a new potent melanogenesis inhibitor, exhibits a unique mode of action while preserving melanocyte integrity","authors":"Peggy Sextius,&nbsp;Emilie Warrick,&nbsp;Amélie Prévot-Guéguiniat,&nbsp;Guillaume Lereaux,&nbsp;Florence Boirre,&nbsp;Ludwig Baux,&nbsp;Safa Ben Hassine,&nbsp;Jie Qiu,&nbsp;Xiaoming Huang,&nbsp;Jinzhu Xu,&nbsp;Sébastien Grégoire,&nbsp;Shosuke Ito,&nbsp;Kazumasa Wakamatsu,&nbsp;Xavier Marat","doi":"10.1111/pcmr.13168","DOIUrl":"10.1111/pcmr.13168","url":null,"abstract":"<p>Research on new ingredients that can prevent excessive melanin production in the skin while considering efficacy, safety but also environmental impact is of great importance to significantly improve the profile of existing actives on the market and avoid undesirable side effects. Here, the discovery of an innovative technology for the management of hyperpigmentation is described. High-throughput screening tests on a wide chemical diversity of molecules and in silico predictive methodologies were essential to design an original thiopyridinone backbone and select 2-mercaptonicotinoyl glycine (2-MNG) as exhibiting the most favorable balance between the impact on water footprint, skin penetration potential and performance. The effectiveness of 2-MNG was confirmed by topical application on pigmented reconstructed epidermis and human skin explants. In addition, experiments have shown that unlike most melanogenesis inhibitors on the market, this molecule is not a tyrosinase inhibitor. 2-MNG binds to certain melanin precursors, preventing their integration into growing melanin and leading to inhibition of eumelanin and pheomelanin synthesis, without compromising the integrity of melanocytes.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"462-479"},"PeriodicalIF":4.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma","authors":"Stephan Forchhammer,&nbsp;Valentin Aebischer,&nbsp;Daniela Lenders,&nbsp;Christian M. Seitz,&nbsp;Christopher Schroeder,&nbsp;Alexandra Liebmann,&nbsp;Michael Abele,&nbsp;Hannah Wild,&nbsp;Ewa Bien,&nbsp;Malgorzata Krawczyk,&nbsp;Dominik T. Schneider,&nbsp;Ines B. Brecht,&nbsp;Lukas Flatz,&nbsp;Matthias Hahn","doi":"10.1111/pcmr.13167","DOIUrl":"10.1111/pcmr.13167","url":null,"abstract":"<p>Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18–30 years; <i>n</i> = 32), adult melanoma (&gt;30 years, <i>n</i> = 30), and benign melanocytic nevi in children (0–18 years; <i>n</i> = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression &gt;75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 4","pages":"453-461"},"PeriodicalIF":4.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}