Skin cancer articles within Nature Communications

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  • Article
    | Open Access

    The role of reciprocal tumour-stroma interactions in tumour invasion remains poorly characterised. Here, single-cell and spatial transcriptomics identifies the cell populations and their transcriptional reprogramming contributing to the spatial organization of the basal cell carcinoma invasive niche.

    • Laura Yerly
    • , Christine Pich-Bavastro
    •  & François Kuonen

  • Article
    | Open Access

    While cutaneous melanoma is linked to UV radiation, acral melanoma is not. Epigenetic mechanisms function as sensors to exposures and determinants of cell identity. Here, the authors use DNA methylation data to identify dysregulated pathways associated with UV radiation and pathobiology in cutaneous and acral melanomas.

    • Anna Luiza Silva Almeida Vicente
    • , Alexei Novoloaca
    •  & Akram Ghantous

  • Article
    | Open Access

    The regulation of the distinct intrinsic phenotypic states in melanoma remain poorly characterised. Here, multi-omics analysis for a panel of 68 early passage melanoma cell lines reveals that cancer cell intrinsic transcriptomic programs are associated with distinct immune features.

    • Miles C. Andrews
    • , Junna Oba
    •  & Scott E. Woodman

  • Article
    | Open Access

    Activating mutations of BRAF alone are inadequate to drive melanoma formation. Here the authors show that activation of Hippo signalling by oncogenic BRAF represents an additional safeguard to limit BRAF-dependent human melanocyte growth and melanoma formation.

    • Marc A. Vittoria
    • , Nathan Kingston
    •  & Neil J. Ganem

  • Article
    | Open Access

    The factors that determine the distinct profiles of NRAS mutants across different tumor types remain unclear. Here, the authors use an allelic series of conditional mouse models to investigate the molecular mechanisms underlying the enrichment of specific NRAS mutants in human melanoma

    • Brandon M. Murphy
    • , Elizabeth M. Terrell
    •  & Christin E. Burd

  • Article
    | Open Access

    The identification of somatic point mutations in tumor samples is of high clinical value, such as for the development of targeted therapies. Here the authors develop a machine learning pipeline for detecting somatic point mutations from RNA sequencing without a matched-normal sample, and utilize the model's prediction for computing the tumor mutational burden.

    • Rotem Katzir
    • , Noam Rudberg
    •  & Keren Yizhak

  • Article
    | Open Access

    Slow-cycling melanoma persister cells are characterised by a high, reversible expression of H3K4 demethylase KDM5B. Here, the authors use genetic and chemical methods to enforce a permanent high expression of KDM5B and show that these cells transit to a melanocytic differentiated state and undergo cell cycle arrest.

    • Heike Chauvistré
    • , Batool Shannan
    •  & Alexander Roesch

  • Article
    | Open Access

    The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.

    • Wenji Piao
    • , Lushen Li
    •  & Jonathan S. Bromberg

  • Article
    | Open Access

    The IFNγ response pathway is associated with response to immunotherapy in cancer. Here the authors show that high levels of the IFNγ-receptor (IFNγ-R1) affect the outcome of immunotherapy in a context-dependent fashion and identify the E3 ubiquitin ligase STUB1 as a negative regulator of IFNγ-R1/JAK1 expression in cancer cells.

    • Georgi Apriamashvili
    • , David W. Vredevoogd
    •  & Daniel S. Peeper

  • Article
    | Open Access

    STAG2 is a core subunit of the cohesin complex involved in DNA looping, but its transcriptional targets are largely unknown. Here the authors show STAG2 controls the 3D chromatin structure at the IRF9 locus to restrict IRF9 expression. Loss of STAG2 results in IRF9 activation, which in turn upregulates PD-L1 expression in cancer cells, suggesting a tumor suppressor function in immune evasion.

    • Zhaowei Chu
    • , Lei Gu
    •  & Bin Zheng

  • Article
    | Open Access

    Cutaneous T cell lymphomas (CTCL) are still poorly characterised at the molecular and single-cell level. Here, the authors analyse CTCL patient samples using single-cell RNA-seq, TCR and whole-exome sequencing, revealing the molecular profiles of malignant T cells and their association with the microenvironment and clinical outcomes.

    • Xiangjun Liu
    • , Shanzhao Jin
    •  & Yang Wang

  • Article
    | Open Access

    Despite acral melanoma being the most common melanoma subtype in non-White individuals, its molecular drivers remain unknown. Here, the authors integrate genomic and clinical data from 104 patients and identify late-arising focal amplifications of chr22q11.21 and LZTR1 as a key tumour promoter in this region.

    • Farshad Farshidfar
    • , Kahn Rhrissorrakrai
    •  & Ruth Halaban

  • Article
    | Open Access

    Whether intermittent strategies of delivering drugs can improve cancer patients survival is still unclear. Here, the authors reports the results of a randomized phase II clinical trial aimed to compare the efficacy and safety of two dosing regimens (continuous and intermittent) of vemurafenib and cobimetinib combination as first-line treatment of patients with unresectable or metastatic advanced melanoma with BRAFV600 mutation

    • Maria Gonzalez-Cao
    • , Clara Mayo de las Casas
    •  & Alfonso Berrocal

  • Article
    | Open Access

    Gene signatures that predict response to immune checkpoint blockade (ICB) therapies in melanoma have been based on preclinical models and pre-treatment samples. Here the authors develop pathway-based signatures to predict ICB response in melanoma using on-treatment samples, leading to improved performance.

    • Kuang Du
    • , Shiyou Wei
    •  & Gao Zhang

  • Article
    | Open Access

    The acidic tumour microenvironment in melanoma drives immune evasion by cAMP in tumor-infiltrating monocytes. Here, the authors show that the release of an adenylate cyclase inhibitor from micelles restores antitumor immunity and, when combined with regulatory T cell depletion, leads to remission of established B16-F10-OVA tumors.

    • Kerstin Johann
    • , Toszka Bohn
    •  & Christian Becker

  • Article
    | Open Access

    Melanoma cells can switch between proliferative and invasive phenotypes. Here the authors show that the embryonic stem cell factor Sall4 is a negative regulator of melanoma phenotype switching where its loss leads to the acquisition of an invasive phenotype, due to derepression of invasiveness genes.

    • Johanna Diener
    • , Arianna Baggiolini
    •  & Lukas Sommer

  • Article
    | Open Access

    The relevance and underlying molecular mechanisms of epigenetic regulation in squamous cell carcinomas (SCC) await further characterization. Here, the authors show a transcriptional regulatory loop involving SREBF1, TP63 and KLF5 driving tumourigenesis in SCC through fatty acid, ERBB and mTOR pathway regulation.

    • Li-Yan Li
    • , Qian Yang
    •  & De-Chen Lin

  • Article
    | Open Access

    The transcription factor BRN2 regulates melanoma migration and invasion, but its role during melanoma initiation is unclear. Here the authors show that BRN2 is a haplo-insufficient tumour suppressor that positively regulates PTEN expression and in the context of BRAF mutation and heterozygous PTEN, BRN2 loss promotes melanoma initiation and progression.

    • Michael Hamm
    • , Pierre Sohier
    •  & Lionel Larue

  • Article
    | Open Access

    Ultraviolet radiation (UVR) increases melanoma incidence. Here, the authors report that UVR-damaged dermal fibroblasts upregulate MMP1 to degrade collagen which inhibits melanoma invasion and that aged primary melanomas in skin with degraded collagen have a better prognosis, while new collagen synthesis restores invasion and leads to death.

    • Timothy Budden
    • , Caroline Gaudy-Marqueste
    •  & Amaya Virós

  • Article
    | Open Access

    The absence of scaffold protein Ambra1 leads to hyperproliferation and growth in mouse models. Here the authors show that Ambra1 deficiency accelerates melanoma growth and increases metastasis in mouse models of melanoma through FAK1 hyperactivation.

    • Luca Di Leo
    • , Valérie Bodemeyer
    •  & Francesco Cecconi

  • Article
    | Open Access

    Metastasis is one of the leading causes of cancer-related death. Here, the authors report a pro-metastatic role of PRAK in breast cancer lung metastasis via a mechanism involving enhanced HIF-1α translation, and propose PRAK targeting as a strategy to treat metastasis.

    • Yuqing Wang
    • , Wei Wang
    •  & Yu Zhang

  • Article
    | Open Access

    Epigenetic mechanisms associated with the differentiation state of cancer cells and their heterogeneity influence tumor responses to oncogene-targeted therapies. In this study, the authors perform an epigenetic compound screen and single-cell analysis in BRAF-mutant melanoma cells to identify compounds that block three distinct drug-tolerant epigenetic states associated with either one of the lysine-specific histone demethylases Kdm1a or Kdm4b, or BET proteins.

    • Mehwish Khaliq
    • , Mohan Manikkam
    •  & Mohammad Fallahi-Sichani

  • Article
    | Open Access

    Checkpoint blocking therapies are used to treat metastatic melanoma, but can have adverse immune-mediated effects, including liver pathology. Here the authors identify an expanded pool of CD4+ effector memory T cells resulting from prior CMV exposure as a risk factor for this adverse effect in these patients.

    • James A. Hutchinson
    • , Katharina Kronenberg
    •  & Sebastian Haferkamp

  • Article
    | Open Access

    It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation.

    • Chen Jiang
    • , Ahsan Javed
    •  & Thomas Worzfeld

  • Article
    | Open Access

    The identification of prognostic biomarkers can help stratify cancer patients. Here, the authors apply deep RNA sequencing from primary melanomas coupled with long-term clinical outcome data from a prospective multicentre phase III trial, to develop and validate a 121 metastasis-associated gene signature identifying early-stage melanoma patients at higher risk of metastasis and worse survival.

    • Manik Garg
    • , Dominique-Laurent Couturier
    •  & Roy Rabbie

  • Article
    | Open Access

    Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.

    • Rajasekharan Somasundaram
    • , Thomas Connelly
    •  & Meenhard Herlyn

  • Article
    | Open Access

    Mucosal melanomas are not thought to be UV radiation (UVR)-driven, yet some present UVR-related mutations. Here the authors show that some mucosal melanomas, especially conjunctival, present mutations characteristic of UVR exposure, yet share structural variants typical of other mucosal melanomas.

    • Piyushkumar A. Mundra
    • , Nathalie Dhomen
    •  & Richard Marais

  • Article
    | Open Access

    Predicting who will develop skin cancer is difficult. Here, the authors from 23andMe developed a polygenic risk score for skin cancer based on a questionnaire and genetic data from more than 210,000 individuals and suggest that the score could be used in early screening programmes.

    • Pierre Fontanillas
    • , Babak Alipanahi
    •  & Adam Auton

  • Article
    | Open Access

    IL-2/anti-IL-2 complexes have been proposed to curtail the severe adverse effects associated with IL-2 immunotherapy. Here, the authors, by integrating unmutated human IL-2 in the antigen binding groove of an anti-IL-2 monoclonal antibody, generate a CD122-biased fusion protein that prevents binding of IL-2 to CD25 and promotes anti-tumor immune response in several preclinical metastatic cancer models.

    • Dilara Sahin
    • , Natalia Arenas-Ramirez
    •  & Onur Boyman

  • Article
    | Open Access

    Resistance to BRAF/MEK inhibitors is a major impediment to long-term survival for patients with BRAF-mutant melanomas. Here, the authors show that ABL kinases drive resistance by promoting MEK/ERK reactivation and the FDA-approved ABL kinase inhibitor nilotinib prevents and overcomes resistance.

    • Rakshamani Tripathi
    • , Zulong Liu
    •  & Rina Plattner

  • Article
    | Open Access

    Acral melanoma occurs on the soles of the feet, palms of the hands and in nail beds. Here, the authors reports the genomic landscape of 87 acral melanomas and find that some tumors harbor a UV signature and that the tumors are diverse at the levels of mutational signatures, structural aberrations and copy number signatures.

    • Felicity Newell
    • , James S. Wilmott
    •  & Nicholas K. Hayward

  • Article
    | Open Access

    The presence of genomic alterations in cancer associated fibroblasts (CAFs) is largely unexplored. The authors show that frequent NOTCH1 gene amplification and overexpression render CAFs resistant to the UVA-induced DNA damage response (DDR) and promote cancer/stromal cells expansion, which can be reversed by NOTCH inhibition.

    • Atul Katarkar
    • , Giulia Bottoni
    •  & G. Paolo Dotto

  • Article
    | Open Access

    Basal cell carcinoma (BCC) cells with increased nuclear myocardin-related transcription factor (nMRTF) levels are resistant to Smoothened inhibitors, however how MRTF activity is regulated is still elusive. Here, the authors identify a LYPD3+/TACSTD2+/LY6D+ BCC subpopulation of resistant BCC cells where AP-1 and TGFß drive nMRTF activation and amplify noncanonical Gli1 activity

    • Catherine D. Yao
    • , Daniel Haensel
    •  & Anthony E. Oro

  • Article
    | Open Access

    Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.

    • Roy Rabbie
    • , Naser Ansari-Pour
    •  & David J. Adams

  • Article
    | Open Access

    Dedifferentiation state has been associated with therapy resistance in melanoma. Here, the authors uncover a pre-existing NGFR-expressing, targetable subpopulation that is resistant to immunotherapy and other treatments in melanoma cells and preclinical models.

    • Julia Boshuizen
    • , David W. Vredevoogd
    •  & Daniel S. Peeper

  • Article
    | Open Access

    The transcripts generated by frameshifts and indels in cancer are frequently degraded by nonsense mediated decay. Here, the authors show that some of these transcripts can escape this degradation mechanism and their prevalence correlates with tumour response to immunotherapy.

    • Kevin Litchfield
    • , James L. Reading
    •  & Charles Swanton

  • Review Article
    | Open Access

    Despite the new targeted and immunotherapies for metastatic melanoma, several patients show therapeutic plateau. Here, the authors review the current pre-clinical models of cutaneous melanoma and discuss their strengths and limitations that may help with overcoming therapeutic plateau.

    • Vito W. Rebecca
    • , Rajasekharan Somasundaram
    •  & Meenhard Herlyn

  • Article
    | Open Access

    Immunopeptidomics allows identifying the cellular repertoire of MHC-bound peptides, but quantifying them remains challenging. Here, the authors present a method to efficiently generate internal peptide MHC standards and calibration curves, facilitating relative and absolute quantitative immunopeptidomics.

    • Lauren E. Stopfer
    • , Joshua M. Mesfin
    •  & Forest M. White

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