Evidence map›Paper›PMID 30797773›Full record

ArticleCell systems2019

Convergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo.

Adan Codina, Paul A Renauer, Guangchuan Wang, Ryan D Chow, Jonathan J Park, Hanghui Ye, Kerou Zhang, Matthew B Dong, Brandon Gassaway, Lupeng Ye and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Opportunities and Challenges of Kava in Lung Cancer Prevention.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
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

19 authors at 2 institutions in 1 country.

Adan CodinaSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; MCGD Program, Yale University, 333 Cedar Street, New Haven, CT 06510, USA.
Paul A RenauerSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; MCGD Program, Yale University, 333 Cedar Street, New Haven, CT 06510, USA.
Guangchuan WangSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA.
Ryan D ChowSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA.
Jonathan J ParkSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA.
Hanghui YeSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA.
Kerou ZhangCenter for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
Matthew B DongSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA.
Brandon GassawaySystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Cellular and Molecular Physiology, Yale University, 333 Cedar St., New Haven, CT 06520, USA.
Lupeng YeSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA.
Youssef ErramiSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA.
Li ShenSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA.
Alan ChangSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA.
Dhanpat JainDepartment of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Roy S HerbstDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA; Smilow Cancer Hospital, 35 Park St, New Haven, CT 06510, USA; Yale Comprehensive Cancer Center, 20 York Street, Ste North Pavilion 4, New Haven, CT 06510, USA.
Marcus BosenbergDepartment of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Comprehensive Cancer Center, 20 York Street, Ste North Pavilion 4, New Haven, CT 06510, USA; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510, USA.
Jesse RinehartSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Cellular and Molecular Physiology, Yale University, 333 Cedar St., New Haven, CT 06520, USA.
Rong FanCenter for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, CT 06511, USA.
Sidi ChenSystem Biology Institute, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, 850 West Campus Drive, West Haven, CT 06516, USA; MCGD Program, Yale University, 333 Cedar Street, New Haven, CT 06510, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA; Yale Comprehensive Cancer Center, 20 York Street, Ste North Pavilion 4, New Haven, CT 06510, USA; Immunobiology Program, The Anlyan Center, 300 Cedar Street, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: sidi.chen@yale.edu.
Yale University · USYale Cancer Center · US

Funding

Yale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI DAVID F STERN · 2006 to 2026
$43.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Shuangge Ma · 2015 to 2026
$31.1M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9M
Systems analysis of phenotypic switch in control of cancer invasionU54CA209992 · NCI · YALE UNIVERSITY · PI LEVCHENKO, ANDRE · 2016 to 2021
$10.1M
GENETICS AND GENOMICS OF HUMAN DISEASET32HD007149 · NICHD · YALE UNIVERSITY · PI James P Noonan · 1985 to 2026
$8.2M
(PQ4) Novel tools for in vivo study of genetic interactions in cancer progressionR01CA231112 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2022
$3.0M
High-throughput in vivo genetics for immunotherapy target discoveryDP2CA238295 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2018
$2.5M
Rapidly scalable platforms for direct in vivo screening of functional drivers in lethal cancersR33CA225498 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2019 to 2021
$1.2M
High Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890k
NCI NIH HHS DP2 CA238295NCI NIH HHS P50 CA121974NCI NIH HHS P50 CA196530NCI NIH HHS R01 CA231112NCI NIH HHS R33 CA225498NCI NIH HHS U54 CA209992NICHD NIH HHS T32 HD007149NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007499NIH HHS S10 OD018521
6 · The paper itself

Abstract

The genetic makeup of cancer cells directs oncogenesis and influences the tumor microenvironment. In this study, we massively profiled genes that functionally drive tumorigenesis using genome-scale in vivo CRISPR screens in hosts with different levels of immunocompetence. As a convergent hit from these screens, Prkar1a mutant cells are able to robustly outgrow as tumors in fully immunocompetent hosts. Functional interrogation showed that Prkar1a loss greatly altered the transcriptome and proteome involved in inflammatory and immune responses as well as extracellular protein production. Single-cell transcriptomic profiling and flow cytometry analysis mapped the tumor microenvironment of Prkar1a mutant tumors and revealed the transcriptomic alterations in host myeloid cells. Taken together, our data suggest that tumor-intrinsic mutations in Prkar1a lead to drastic alterations in the genetic program of cancer cells, thereby remodeling the tumor microenvironment.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsGene Expression ProfilingNeoplasmscancer genomicscancer immunologyin vivo CRISPR screenPrkar1atransformation

Identifiers

PMID30797773
PMCPMC6592847
OpenAlexW2917588260

What OpenQuestion holds

Textmetadata
LicenceTDM
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.