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SpaceBar is a cellular barcoding strategy for simultaneous analysis of cell clonal and spatial identities.

It has been reported that the circadian clock regulator Bmal1 can modulate tumorigenesis. Here the authors show that ectopic expression of Bmal1 promotes an immune resistant mesenchymal melanoma cell state associated with increased AP-1 activity.

Mechanisms underlying tumor cell plasticity remain poorly understood. Here, the authors show the presence of a dormant-invasive SOX10- subpopulation in cutaneous melanoma that can be targeted by cIAP1/2 inhibitors.

Prolyl hydroxylase domain protein 2 (PHD2) regulates cellular response to hypoxia. Here the authors show that PHD2 is downregulated in melanoma and that PHD2 depletion, in a mouse model, promotes the progression of benign melanocytic lesions into melanoma, via activation of the Akt/mTOR signaling cascade.

Anti-cancer treatment often results in a subset of the clonal cell population developing resistance to therapy, with resistant cells displaying a diversity of fate types resulting from the intrinsic variability among the clonal population before treatment.

Resistance to BRAFV600E inhibitors often occurs in melanoma patients. Here, the authors describe a potential mechanism of acquired drug resistance mediated by tumor-associated B cells-derived IGF-1.

A class of compounds with a dual mechanism of action—direct targeting of IspH and stimulation of cytotoxic γδ T cells to enhance pathogen clearance—are active against multidrug-resistant bacteria.

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.

A new study shows that melanoma-derived exosomes contribute to metastatic invasion by carrying messenger proteins that direct bone marrow–derived cells toward a prometastatic phenotype. This leads to the promotion of proangiogenic events and modification of the extracellular matrix at premetastatic sites (pages 883–891).

Sun exposure indisputably increases the risk of skin cancer. Mouse studies suggest that, in red-haired individuals, genetic factors also contribute through a mechanism that acts independently of exposure to sunlight. See Letter p.449

Melanoma cells release programmed death-ligand 1 (PD-L1) on the surface of circulating exosomes, suggesting a mechanism by which tumours could evade the immunesystem, and the potential application of exosomal PD-L1 to monitor patient responses to checkpoint therapies.

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.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

BRAF-inhibition resistance in metastatic melanoma occurs through p21-activated kinase-mediated reactivation of ERK, whereas resistance to combined BRAF and MEK inhibition occurs through p21-activated kinase-mediated regulation of JNK and β-catenin phosphorylation, mTOR pathway activation and apoptosis inhibition in many patients.

Some skin pigment disorders such as vitiligo are caused by the loss of melanocytes, the pigment-producing cells in the skin. Here the authors present an approach to directly convert mouse and human dermal fibroblasts into functional melanocytes.

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.

ClampFISH 2.0 enables highly specific multiplexed signal amplification in RNA FISH. The approach was used to detect 10 RNA species that ranged in abundance in more than 1 million cells and is also applicable to tissue sections.

Lack of CD8⁺ T-cell infiltration into solid tumors is associated with poor responsiveness to immune checkpoint therapy (ICT). Here, the authors show that blocking the phosphorylation of HRS to reduce the induction of immunosuppressive exosomes promotes CD8⁺ T-cell infiltration into tumors and enhances the efficacy of ICT in mouse melanoma models.

Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.

Zhu et al. report that, in response to growth signals, ERK undergoes TRIM15-mediated lysine-63-linked ubiquitination, which facilitates ERK interaction with MEK and therefore enhances ERK activity.

The regulation of tumor inflammation is incompletely understood and the role of B cells is unclear. Here, the authors show that a specific subtype of B cells is induced in melanoma and required to recruit T lymphocytes and elicit inflammation.

Transplantation of metastatic melanoma cells into zebrafish embryo disrupts development—and identifies a potential new drug target for this deadly cancer (pages 925–932).

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

Genetic and protein expression analyses of serially collected tumor biopsies from a patient with melanoma treated with immune checkpoint inhibitors provide insights into tumor microenvironment changes that occur during treatment resistance.