Evidence map›Paper›PMID 36669486›Full record

ArticleCancer cell2023

Base editing screens map mutations affecting interferon-γ signaling in cancer.

Matthew A Coelho, Sarah Cooper, Magdalena E Strauss, Emre Karakoc, Shriram Bhosle, Emanuel Gonçalves, Gabriele Picco, Thomas Burgold, Chiara M Cattaneo, Vivien Veninga and 12 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
13.9field-weighted citation impact, top 1% of its field
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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
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  11. Inhibition of LDHA promotes GSDME-dependent pyroptosis by activating RIG-I-like receptor signaling.Apoptosis : an international journal on programmed cell death · 2026
    Article
  12. Review
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  20. Genetic mechanisms of resistance to targeted KRAS inhibition.bioRxiv : the preprint server for biology · 2025
    Article

3 more citing papers are in PubMed but not listed here.

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

22 authors at 5 institutions in 3 countries.

Matthew A CoelhoTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Sarah CooperGene Editing and Cellular Research and Development, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Magdalena E StraussEMBL-European Bioinformatics Institute, Cambridge, UK.
Emre KarakocTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Shriram BhosleTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK.
Emanuel GonçalvesTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Instituto Superior Técnico, Universidade de Lisboa, 1049-001, and, INESC-ID, 1000-029, Lisbon, Portugal.
Gabriele PiccoTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Thomas BurgoldGene Editing and Cellular Research and Development, Wellcome Sanger Institute, Hinxton, UK.
Chiara M CattaneoDepartment of Immunology and Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Open Targets, Cambridge, UK.
Vivien VeningaDepartment of Immunology and Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Open Targets, Cambridge, UK.
Sarah ConsonniTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Cansu DinçerTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK.
Sara F VieiraTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Freddy GibsonTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK.
Syd BarthorpeTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK.
Claire HardyCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Hinxton, UK.
Joel ReinCellular Operations and Stem Cell Informatics, Wellcome Sanger Institute, Hinxton, UK.
Mark ThomasCellular Operations and Stem Cell Informatics, Wellcome Sanger Institute, Hinxton, UK.
John MarioniEMBL-European Bioinformatics Institute, Cambridge, UK.
Emile E VoestDepartment of Immunology and Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Oncode Institute, Utrecht, the Netherlands; Open Targets, Cambridge, UK.
Andrew BassettGene Editing and Cellular Research and Development, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK.
Mathew J GarnettTranslational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK; Open Targets, Cambridge, UK. Electronic address: mathew.garnett@sanger.ac.uk.
Wellcome Sanger Institute · GBOpen Targets · GBEuropean Bioinformatics Institute · GBInstituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento · PTOncode Institute · NL

Funding

Wellcome TrustWellcome Trust 220442/Z/20/Z
6 · The paper itself

Abstract

Interferon-γ (IFN-γ) signaling mediates host responses to infection, inflammation and anti-tumor immunity. Mutations in the IFN-γ signaling pathway cause immunological disorders, hematological malignancies, and resistance to immune checkpoint blockade (ICB) in cancer; however, the function of most clinically observed variants remains unknown. Here, we systematically investigate the genetic determinants of IFN-γ response in colorectal cancer cells using CRISPR-Cas9 screens and base editing mutagenesis. Deep mutagenesis of JAK1 with cytidine and adenine base editors, combined with pathway-wide screens, reveal loss-of-function and gain-of-function mutations, including causal variants in hematological malignancies and mutations detected in patients refractory to ICB. We functionally validate variants of uncertain significance in primary tumor organoids, where engineering missense mutations in JAK1 enhanced or reduced sensitivity to autologous tumor-reactive T cells. We identify more than 300 predicted missense mutations altering IFN-γ pathway activity, generating a valuable resource for interpreting gene variant function.

Indexed as

Hematologic NeoplasmsNeoplasmsCRISPR-Cas SystemsGene EditingHumansInterferon-gammaMutationSignal TransductionInterferon-gammabase editingcancer geneticscancer immunotherapydrug resistancefunctional genomicsgene editingIFN-γ signalinginterferon gammavariants of uncertain significance

Identifiers

PMID36669486
PMCPMC9942875
OpenAlexW4317689970

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.