Evidence map›Paper›PMID 35276062›Full record

ArticleCell metabolism2022

A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy.

Lupeng Ye, Jonathan J Park, Lei Peng, Quanjun Yang, Ryan D Chow, Matthew B Dong, Stanley Z Lam, Jianjian Guo, Erting Tang, Yueqi Zhang and 10 more

Abstract read
In one paragraph

Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 1 pooled it
–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

141 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  7. Article
  8. Article
  9. Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

81 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

20 authors.

Lupeng YeSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Jonathan J ParkSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA; Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT 06510, USA; MCGD Program, Yale University, New Haven, CT 06510, USA.
Lei PengSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Quanjun YangSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Ryan D ChowSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA; Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT 06510, USA; MCGD Program, Yale University, New Haven, CT 06510, USA.
Matthew B DongSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA; Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT 06510, USA; MCGD Program, Yale University, New Haven, CT 06510, USA; Immunobiology Program, Yale University, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Stanley Z LamSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA; The College, Yale University, New Haven, CT 06520, USA.
Jianjian GuoSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA; Yale M.D.-Ph.D. Program, 367 Cedar Street, New Haven, CT 06510, USA; Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT 06510, USA; MCGD Program, Yale University, New Haven, CT 06510, USA.
Erting TangSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Yueqi ZhangSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Guangchuan WangSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Xiaoyun DaiSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Yaying DuSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Hyunu R KimSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Hanbing CaoSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Youssef ErramiSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Paul ClarkSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA.
Alexey BersenevAdvanced Cell Therapy Laboratory, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Ruth R MontgomeryDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Epidemiology of Microbial Diseases, Yale University School of Public Health, New Haven, CT 06520, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Rheumatology, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT, USA; Comprehensive Cancer Center, Yale University, New Haven, CT 06510, USA.
Sidi ChenSystem Biology Institute, Integrated Science & Technology Center, West Haven, CT 06516, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT 06516, USA; Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT 06510, USA; MCGD Program, Yale University, New Haven, CT 06510, USA; Immunobiology Program, Yale University, New Haven, CT 06520, USA; Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT, USA; Comprehensive Cancer Center, Yale University, New Haven, CT 06510, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA; Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA; Center for RNA Science and Medicine, Yale University, New Haven, CT 06510, USA. Electronic address: sidi.chen@yale.edu.

Funding

Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI David A. Hafler, RUTH R MONTGOMERY · 2010 to 2026
$50.4M
Yale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI RUTH HALABAN · 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 Kurt A Schalper · 2015 to 2026
$31.1M
Short-Term Reserch Training: Students in Health SchoolsT35HL007649 · NHLBI · YALE UNIVERSITY · PI Sarwat I Chaudhry, Erica L Herzog · 1987 to 2026
$5.7M
(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
New approaches for single cell tagging, editing and profiling of glial cells in vivoRF1DA048811 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HONG, WEIZHE · 2019 to 2019
$2.4M
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
Mechanosensation in tumorigenesis and metastasisF30CA250249 · NCI · YALE UNIVERSITY · PI CHOW, RYAN D · 2020 to 2022
$113k
NCI NIH HHS DP2 CA238295NCI NIH HHS F30 CA250249NCI NIH HHS P50 CA121974NCI NIH HHS P50 CA196530NCI NIH HHS R01 CA231112NCI NIH HHS R33 CA225498NHLBI NIH HHS T35 HL007649NIAID NIH HHS U19 AI089992NIDA NIH HHS RF1 DA048811NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-T cell-based immunotherapy for cancer and immunological diseases has made great strides, but it still faces multiple hurdles. Finding the right molecular targets to engineer T cells toward a desired function has broad implications for the armamentarium of T cell-centered therapies. Here, we developed a dead-guide RNA (dgRNA)-based CRISPR activation screen in primary CD8

Indexed as

NeoplasmsReceptors, Chimeric AntigenCD8-Positive T-LymphocytesClustered Regularly Interspaced Short Palindromic RepeatsGain of Function MutationHumansProlineProlineReceptors, Chimeric Antigenantitumor efficacyCAR-Tdead-guide RNAmetabolismmitochondriaPRODH2proline metabolismT cell CRISPR activation screenT cell GOF screen

Identifiers

PMID35276062
PMCPMC8986623

What OpenQuestion holds

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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.