Evidence map›Paper›PMID 35338135›Full record

ArticleNature communications2022

CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity.

Julia Joung, Paul C Kirchgatterer, Ankita Singh, Jang H Cho, Suchita P Nety, Rebecca C Larson, Rhiannon K Macrae, Rebecca Deasy, Yuen-Yi Tseng, Marcela V Maus and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
10.9field-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

77 citing papers in PubMed, 107 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  20. Article

17 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

11 authors at 2 institutions in 1 country.

Julia JoungDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA. julia@joung.science.ORCID 0000-0001-8133-8510
Paul C KirchgattererDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
Ankita SinghDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
Jang H ChoDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
Suchita P NetyDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.ORCID 0000-0002-4201-1061
Rebecca C LarsonDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Rhiannon K MacraeDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
Rebecca DeasyBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID 0000-0001-9143-6296
Yuen-Yi TsengBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Marcela V MausDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7578-0393
Feng ZhangDepartment of Biological Engineering, MIT, Cambridge, MA, 02139, USA. zhang@broadinstitute.org.ORCID 0000-0003-0178-7995
Broad Institute · USHarvard University · US

Funding

Programmable RNA-targeting toolsR01HG009761 · NHGRI · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2017 to 2024
$7.5M
TRAINING IN TRANSPLANTATION BIOLOGYT32AI007529 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI MADSEN, JOREN C · 1998 to 2024
$6.4M
Exploration of Diverse Mobile Genetic Elements for Precision Genome ManipulationDP1HL141201 · NHLBI · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2017 to 2021
$6.2M
Genome-scale transcription factor screen for neural differentiationF31MH117886 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JOUNG, JULIA · 2018 to 2019
$90k
Howard Hughes Medical InstituteNHGRI NIH HHS R01 HG009761NHLBI NIH HHS DP1 HL141201NIAID NIH HHS T32 AI007529NIMH NIH HHS F31 MH117886
6 · The paper itself

Abstract

The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, here we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (CD274 (PD-L1), MCL1, JUNB, and B3GNT2) conferred resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway. JUNB encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-κB pathway. B3GNT2 encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interactions between tumor and T cells and reduce T cell activation. Inhibition of candidate genes sensitized tumor models to T cell cytotoxicity. Our results demonstrate that systematic gain-of-function screening can elucidate resistance pathways and identify potential targets for cancer immunotherapy.

Indexed as

MelanomaProto-Oncogene Proteins c-bcl-2AnimalsApoptosisCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsHumansMiceMyeloid Cell Leukemia Sequence 1 ProteinN-AcetylglucosaminyltransferasesB3GNT2 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinN-AcetylglucosaminyltransferasesProto-Oncogene Proteins c-bcl-2

Identifiers

PMID35338135
PMCPMC8956604
OpenAlexW4220735010

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.