Evidence map›Paper›PMID 27521269›Full record

ArticleImmunity2016

Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis.

Andrea Schietinger, Mary Philip, Varintra E Krisnawan, Edison Y Chiu, Jeffrey J Delrow, Ryan S Basom, Peter Lauer, Dirk G Brockstedt, Sue E Knoblaugh, Günter J Hämmerling and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 451 papers.

0numbers the graph read from it
0cells of the map it votes in
451citing papers in PubMed
22.5field-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

451 citing papers in PubMed, 714 citations in OpenAlex.

  1. Trial
  2. Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Trial
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. TOX drives CD4Nature immunology · 2026
    Article
  17. Adoptive T-cell therapies in the clinic.Bioengineering & translational medicine · 2026
    Review
  18. Article
  19. Article
  20. Review

391 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

13 authors at 7 institutions in 2 countries.

Andrea SchietingerImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Immunology, University of Washington, Seattle, WA 98109, USA; Program of Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: schietia@mskcc.org.
Mary PhilipImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Division of Hematology, University of Washington, Seattle, WA 98195, USA.
Varintra E KrisnawanImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Edison Y ChiuDepartment of Immunology, University of Washington, Seattle, WA 98109, USA.
Jeffrey J DelrowGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Ryan S BasomGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Peter LauerAduro BioTech, Inc., Berkeley, CA 94710, USA.
Dirk G BrockstedtAduro BioTech, Inc., Berkeley, CA 94710, USA.
Sue E KnoblaughComparative Medicine Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Günter J HämmerlingDivisions of Cellular and Molecular Immunology, DKFZ, 69120 Heidelberg, Germany.
Todd D SchellDepartment of Microbiology & Immunology, Penn State Hershey College of Medicine, Hershey, PA 17033, USA.
Natalio GarbiDivisions of Cellular and Molecular Immunology, DKFZ, 69120 Heidelberg, Germany; Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, 53127 Bonn, Germany.
Philip D GreenbergDepartment of Immunology, University of Washington, Seattle, WA 98109, USA; Program of Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: pgreen@uw.edu.
Fred Hutch Cancer Center · USAduro BioTech (United States) · USMemorial Sloan Kettering Cancer Center · USUniversity of Washington · USDKFZ-ZMBH Alliance · DEHeidelberg University · DEPenn State Milton S. Hershey Medical Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Mechanisms of Murine Turmor Eradication by ImmunotherapyR01CA033084 · NCI · UNIVERSITY OF WASHINGTON · PI GREENBERG, PHILIP D · 1986 to 2017
$5.8M
The Role of Heme Metabolic Pathways in T Cell Development and T Cell LymphomageneK08CA158069 · NCI · UNIVERSITY OF WASHINGTON · PI PHILIP, MARY · 2011 to 2015
$837k
Molecular and Epigenetic Programs Underlying T cell Tolerance to Tumor AntigensR00CA172371 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SCHIETINGER, ANDREA · 2015 to 2017
$747k
Chromatin states encoding fate commitment and plasticity of tolerant CD8 T cellsR21AI107776 · NIAID · UNIVERSITY OF WASHINGTON · PI GREENBERG, PHILIP D · 2013 to 2014
$413k
Molecular and Epigenetic Programs Underlying T cell Tolerance to Tumor AntigensK99CA172371 · NCI · UNIVERSITY OF WASHINGTON · PI SCHIETINGER, ANDREA · 2013 to 2014
$340k
NCI NIH HHS K08 CA158069NCI NIH HHS K99 CA172371NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NCI NIH HHS R00 CA172371NCI NIH HHS R01 CA033084NIAID NIH HHS R21 AI107776
6 · The paper itself

Abstract

CD8(+) T cells recognizing tumor-specific antigens are detected in cancer patients but are dysfunctional. Here we developed a tamoxifen-inducible liver cancer mouse model with a defined oncogenic driver antigen (SV40 large T-antigen) to follow the activation and differentiation of naive tumor-specific CD8(+) T (TST) cells after tumor initiation. Early during the pre-malignant phase of tumorigenesis, TST cells became dysfunctional, exhibiting phenotypic, functional, and transcriptional features similar to dysfunctional T cells isolated from late-stage human tumors. Thus, T cell dysfunction seen in advanced human cancers may already be established early during tumorigenesis. Although the TST cell dysfunctional state was initially therapeutically reversible, it ultimately evolved into a fixed state. Persistent antigen exposure rather than factors associated with the tumor microenvironment drove dysfunction. Moreover, the TST cell differentiation and dysfunction program exhibited features distinct from T cell exhaustion in chronic infections. Strategies to overcome this antigen-driven, cell-intrinsic dysfunction may be required to improve cancer immunotherapy.

Indexed as

AnimalsAntigens, Polyomavirus TransformingCancer VaccinesCarcinogenesisCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedCellular SenescenceDisease Models, AnimalHumansImmunotherapy, AdoptiveLiver NeoplasmsLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicAntigens, Polyomavirus TransformingCancer VaccinesTamoxifen

Identifiers

PMID27521269
PMCPMC5119632
OpenAlexW2514996992

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.