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Open AccessUHRF1/UBE2L6/UBR4-mediated ubiquitination regulates EZH2 abundance and thereby melanocytic differentiation phenotypes in melanoma
Cellular heterogeneity in cancer is linked to disease progression and therapy response, although mechanisms regulating distinct cellular states within tumors are not well understood. We identified melanin pigm...
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Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
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Article
Open AccessImmune checkpoint inhibitors and the risk of major atherosclerotic cardiovascular events in patients with high-risk or advanced melanoma: a retrospective cohort study
Immune checkpoint inhibitors (ICI) are associated with immune-mediated adverse effects, potentially involving any organ. ICI has also been associated with an increased risk of cardiovascular disease in cancer ...
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Article
Open AccessMulti-modal molecular programs regulate melanoma cell state
Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-c...
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Article
Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we...
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Article
Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade
Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into ...
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Article
Open AccessSpatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma
Complex tumor microenvironmental (TME) features influence the outcome of cancer immunotherapy (IO). Here we perform immunogenomic analyses on 67 intratumor sub-regions of a PD-1 inhibitor-resistant melanoma tu...
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Article
Open AccessStroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma
Although immune checkpoint inhibitors (ICIs) have achieved unprecedented results in melanoma, the biological features of the durable responses initiated by these drugs remain unknown. Here we show the genetic ...
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Article
Open AccessSustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade
PD-1 blockade represents a major therapeutic avenue in anticancer immunotherapy. Delineating mechanisms of secondary resistance to this strategy is increasingly important. Here, we identified the deleterious r...
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Article
Author Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma
In the version of this article originally published, there was an error in Fig. 2b. RECIST ORR and pCR were both listed as 25%. RECIST ORR was actually 73%, and pCR was 45%. Also, an author’s name was incorrec...
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Publisher Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma
In the version of this article originally published, there was an error in Fig. 1. In the neoadjuvant phase column, the n values for arms A and B were both reported to be 20. The n values for arms A and B were ac...
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Article
Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma
Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment1; however, optima...
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Predictors of Response to Immune Checkpoint Blockade
Cancer therapy has been revolutionized over the past several years through the use of immunotherapy—with demonstrable success in the treatment of multiple cancer types using immune checkpoint blockade and othe...
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Article
Open AccessPLX8394, a new generation BRAF inhibitor, selectively inhibits BRAF in colonic adenocarcinoma cells and prevents paradoxical MAPK pathway activation
BRAF inhibitors (BRAFi) are standard of care for the treatment of BRAF V600 mutation-driven metastatic melanoma, but can lead to paradoxical activation of the mitogen-activated protein kinase (MAPK) signalling pa...
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Open AccessEfficacy of anti-PD-1 therapy in patients with melanoma brain metastases
There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic.
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Article
Open AccessHallmarks of response to immune checkpoint blockade
Unprecedented advances have been made in the treatment of cancer through the use of immune checkpoint blockade, with approval of several checkpoint blockade regimens spanning multiple cancer types. However, re...
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Open AccessReply to ‘Comment on ‘Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy’’
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Open AccessImmunotherapy resistance: the answers lie ahead – not in front – of us
Mechanisms of innate and adaptive resistance to checkpoint blockade immunotherapy are under intense investigation with a view to broadening the therapeutic potential of this form of treatment. In a recent manu...
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Article
Open AccessSystems analysis identifies miR-29b regulation of invasiveness in melanoma
In many cancers, microRNAs (miRs) contribute to metastatic progression by modulating phenotypic reprogramming processes such as epithelial-mesenchymal plasticity. This can be driven by miRs targeting multiple ...
