Evidence map›Paper›PMID 34582788›Full record

ArticleCell2021

In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target.

Xiaoqing Wang, Collin Tokheim, Shengqing Stan Gu, Binbin Wang, Qin Tang, Yihao Li, Nicole Traugh, Zexian Zeng, Yi Zhang, Ziyi Li and 12 more

Open access · greenAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
10.0field-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

134 citing papers in PubMed, 186 citations in OpenAlex.

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  6. Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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74 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 3 institutions in 2 countries.

Xiaoqing WangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Collin TokheimDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Shengqing Stan GuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Binbin WangDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA.
Qin TangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Yihao LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Nicole TraughDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Zexian ZengDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Yi ZhangDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Ziyi LiDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Boning ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jingxin FuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Tengfei XiaoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Wei LiDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Clifford A MeyerDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jun ChuDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
Peng JiangDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Paloma CejasCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Klothilda LimCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Henry LongCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: myles_brown@dfci.harvard.edu.
X Shirley LiuDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: xsliu@ds.dfci.harvard.edu.
Harvard University · USDana-Farber Cancer Institute · USAnhui University · CN

Funding

Regulators of Cancer Immunotherapy ResponseR01CA234018 · NCI · DANA-FARBER CANCER INST · PI BROWN, MYLES A · 2019 to 2022
$2.3M
NCI NIH HHS R01 CA234018
6 · The paper itself

Abstract

Despite remarkable clinical efficacy of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits for triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that deletion of the E3 ubiquitin ligase Cop1 in cancer cells decreases secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, enhances anti-tumor immunity, and strengthens ICB response. Transcriptomics, epigenomics, and proteomics analyses revealed that Cop1 functions through proteasomal degradation of the C/ebpδ protein. The Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. In addition, deletion of the E3 ubiquitin ligase Cop1 in cancer cells stabilizes C/ebpδ to suppress expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy in TNBC by regulating chemokine secretion and macrophage infiltration in the tumor microenvironment.

Indexed as

ImmunotherapyAnimalsCCAAT-Enhancer-Binding Protein-deltaCell Line, TumorChemokinesChemotaxisClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9Disease Models, AnimalGene LibraryHumansImmune EvasionMacrophagesMiceMice, Inbred BALB CMice, Inbred C57BLCCAAT-Enhancer-Binding Protein-deltaChemokinesCOP1 protein, mouseCRISPR-Associated Protein 9Nuclear ProteinsUbiquitin-Protein LigasesC/ebpδCop1CRISPR screeningE3 ubiquitin ligaseimmunotherapytriple-negative breast cancer

Identifiers

PMID34582788
PMCPMC9136996
OpenAlexW3111243436

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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.