Evidence map›Paper›PMID 39216232›Full record

ArticleEBioMedicine2024

Single-cell RNA sequencing reveals melanoma cell state-dependent heterogeneity of response to MAPK inhibitors.

Su Yin Lim, Yingxin Lin, Jenny H Lee, Bernadette Pedersen, Ashleigh Stewart, Richard A Scolyer, Georgina V Long, Jean Y H Yang, Helen Rizos

Abstract read
PubMed Full text at PMC Publisher
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Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Su Yin LimMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia; Melanoma Institute Australia, Australia. Electronic address: esther.lim@mq.edu.au.
Yingxin LinSchool of Mathematics and Statistics, The University of Sydney, Australia; Charles Perkins Centre, The University of Sydney, Australia.
Jenny H LeeMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia; Melanoma Institute Australia, Australia; Department of Neurosurgery, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
Bernadette PedersenMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia; Melanoma Institute Australia, Australia.
Ashleigh StewartMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia; Melanoma Institute Australia, Australia.
Richard A ScolyerMelanoma Institute Australia, Australia; Charles Perkins Centre, The University of Sydney, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Australia.
Georgina V LongMelanoma Institute Australia, Australia; Charles Perkins Centre, The University of Sydney, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Australia.
Jean Y H YangSchool of Mathematics and Statistics, The University of Sydney, Australia; Charles Perkins Centre, The University of Sydney, Australia.
Helen RizosMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia; Melanoma Institute Australia, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelanoma is a heterogeneous cancer influenced by the plasticity of melanoma cells and their dynamic adaptations to microenvironmental cues. Melanoma cells transition between well-defined transcriptional cell states that impact treatment response and resistance.

methodsIn this study, we applied single-cell RNA sequencing to interrogate the molecular features of immunotherapy-naive and immunotherapy-resistant melanoma tumours in response to ex vivo BRAF/MEK inhibitor treatment.

findingsWe confirm the presence of four distinct melanoma cell states - melanocytic, transitory, neural-crest like and undifferentiated, and identify enrichment of neural crest-like and undifferentiated melanoma cells in immunotherapy-resistant tumours. Furthermore, we introduce an integrated computational approach to identify subsets of responding and nonresponding melanoma cells within the transcriptional cell states.

interpretationNonresponding melanoma cells are identified in all transcriptional cell states and are predisposed to BRAF/MEK inhibitor resistance due to pro-inflammatory IL6 and TNFɑ signalling. Our study provides a framework to study treatment response within distinct melanoma cell states and indicate that tumour-intrinsic pro-inflammatory signalling contributes to BRAF/MEK inhibitor resistance.

fundingThis work was supported by Macquarie University, Melanoma Institute Australia, and the National Health and Medical Research Council of Australia (NHMRC; grant 2012860, 2028055).

Indexed as

Drug Resistance, NeoplasmMelanomaProtein Kinase InhibitorsSequence Analysis, RNASingle-Cell AnalysisCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansProto-Oncogene Proteins B-rafProtein Kinase InhibitorsProto-Oncogene Proteins B-rafComputational biologyDedifferentiationImmunotherapy resistanceMAPK inhibitor resistance

Identifiers

PMID39216232
PMCPMC11402938

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.