Evidence map›Paper›PMID 36007524›Full record

ArticleMed (New York, N.Y.)2022

Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade.

Douglas C Palmer, Beau R Webber, Yogin Patel, Matthew J Johnson, Christine M Kariya, Walker S Lahr, Maria R Parkhurst, Jared J Gartner, Todd D Prickett, Frank J Lowery and 28 more

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

Article in Med (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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  16. IL-2-independent expansion, persistence, and antitumor activity in TIL expressing regulatable membrane-bound IL-15.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  17. Review
  18. Article
  19. Review
  20. TIL Therapy in Lung Cancer: Current Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

38 authors at 5 institutions in 1 country.

Douglas C PalmerSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA. Electronic address: palmerdc33@gmail.com.
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA. Electronic address: webb0178@umn.edu.
Yogin PatelSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Matthew J JohnsonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Christine M KariyaSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Walker S LahrDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Maria R ParkhurstSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Jared J GartnerSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Todd D PrickettSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Frank J LowerySurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Rigel J KishtonSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Devikala GurusamySurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Zulmarie FrancoSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Suman K VodnalaSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Miechaleen D DiersDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Natalie K WolfDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
David H McKennaDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Darin SumstadMolecular and Cellular Therapeutics, University of Minnesota, Saint Paul, MN, USA.
Lydia VineyIntima Bioscience, Inc., New York, NY, USA.
Tom HenleyIntima Bioscience, Inc., New York, NY, USA.
Tilmann BürckstümmerIntima Bioscience, Inc., New York, NY, USA.
Oliver BakerIntima Bioscience, Inc., New York, NY, USA.
Ying HuThe Center for Biomedical Informatics and Information Technology (CBIIT), National Institutes of Health, Bethesda, MD, USA.
Chunhua YanThe Center for Biomedical Informatics and Information Technology (CBIIT), National Institutes of Health, Bethesda, MD, USA.
Daoud MeerzamanThe Center for Biomedical Informatics and Information Technology (CBIIT), National Institutes of Health, Bethesda, MD, USA.
Kartik PadhanNational Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health, Bethesda, MD, USA.
Winnie LoSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Parisa MalekzadehSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Li JiaSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Drew C DenigerSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Shashank J PatelSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Paul F RobbinsSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
R Scott McIvorSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA.
Modassir ChoudhryIntima Bioscience, Inc., New York, NY, USA.
Steven A RosenbergSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA. Electronic address: sar@nih.gov.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA. Electronic address: mori0164@umn.edu.
Nicholas P RestifoSurgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA. Electronic address: restifon@mail.nih.gov.
National Institutes of Health · USNational Cancer Institute · USUniversity of Minnesota · USCenter for Information Technology · USUniversity of Minnesota Medical Center · US

Funding

Multiplex Engineered Human Lymphocytes for Therapeutic Protein DeliveryR21AI163731 · NIAID · UNIVERSITY OF MINNESOTA · PI WEBBER, BEAU RICHARD · 2021 to 2022
$426k
RECOMBINANT AND SYNTHETIC ANTI-CANCER VACCINESZ01SC006670 · SC · CLINICAL SCIENCES · PI RESTIFO, NICHOLAS P · 1996 to 2005
–
Intramural NIH HHS Z01 SC006670NIAID NIH HHS R21 AI163731
6 · The paper itself

Abstract

backgroundAdoptive transfer of tumor-infiltrating lymphocytes (TIL) fails to consistently elicit tumor rejection. Manipulation of intrinsic factors that inhibit T cell effector function and neoantigen recognition may therefore improve TIL therapy outcomes. We previously identified the cytokine-induced SH2 protein (CISH) as a key regulator of T cell functional avidity in mice. Here, we investigate the mechanistic role of CISH in regulating human T cell effector function in solid tumors and demonstrate that CRISPR/Cas9 disruption of CISH enhances TIL neoantigen recognition and response to checkpoint blockade.

methodsSingle-cell gene expression profiling was used to identify a negative correlation between high CISH expression and TIL activation in patient-derived TIL. A GMP-compliant CRISPR/Cas9 gene editing process was developed to assess the impact of CISH disruption on the molecular and functional phenotype of human peripheral blood T cells and TIL. Tumor-specific T cells with disrupted Cish function were adoptively transferred into tumor-bearing mice and evaluated for efficacy with or without checkpoint blockade.

findingsCISH expression was associated with T cell dysfunction. CISH deletion using CRISPR/Cas9 resulted in hyper-activation and improved functional avidity against tumor-derived neoantigens without perturbing T cell maturation. Cish knockout resulted in increased susceptibility to checkpoint blockade in vivo.

conclusionsCISH negatively regulates human T cell effector function, and its genetic disruption offers a novel avenue to improve the therapeutic efficacy of adoptive TIL therapy.

fundingThis study was funded by Intima Bioscience, U.S. and in part through the Intramural program CCR at the National Cancer Institute.

Indexed as

Lymphocytes, Tumor-InfiltratingT-LymphocytesAdoptive TransferAnimalsCytokinesHumansImmunotherapy, AdoptiveMiceCytokinescancercheckpointCISHCRISPRimmunotherapyneoantigenPD-1preclinical researchscRNAseqT cell therapyTIL

Identifiers

PMID36007524
PMCPMC9847506
OpenAlexW4292951383

What OpenQuestion holds

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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.