Evidence map›Paper›PMID 27084739›Full record

ReviewClinical cancer research : an official journal of the American Association for Cancer Research2016

Reversing T-cell Dysfunction and Exhaustion in Cancer.

Hassane M Zarour

Open access · greenAbstract readReview
In one paragraph

Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 278 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
278citing papers in PubMed, 2 pooled it
19.2field-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

278 citing papers in PubMed, 2 syntheses or guidelines pooled it, 462 citations in OpenAlex.

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  10. TFAP2A links drug resistance to antitumor immunity.bioRxiv : the preprint server for biology · 2026
    Article
  11. Revealing the dynamics of follicular T cells and checkpoint engagement in surgically resected colorectal cancer and their relations to clinicopathological aspects.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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218 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

1 author at 1 institution in 1 country.

Hassane M ZarourDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. zarourhm@upmc.edu.
University of Pittsburgh · US

Funding

Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9M
Reversing melanoma-induced T cell dysfunctionR01CA157467 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZAROUR, HASSANE M · 2011 to 2015
$1.5M
NCI NIH HHS P50 CA121973NCI NIH HHS P50CA121973NCI NIH HHS R01 CA157467NCI NIH HHS R01CA157467
6 · The paper itself

Abstract

In the context of chronic antigen exposure in chronic viral infections and cancer, T cells become exhausted/dysfunctional. These exhausted T cells exhibit defective proliferative capacities and cytokine production, but are not totally inert and may exert lytic functions. Importantly, exhausted T cells upregulate multiple inhibitory receptors/immune checkpoints that bind to their ligands expressed by tumor cells and antigen-presenting cells in the tumor microenvironment (TME). Immune checkpoint blockades with anti-CTL antigen 4 (CTLA-4) and/or anti-programmed death 1 (PD-1) mAbs successfully reinvigorate tumor-infiltrating T lymphocytes and provide persistent clinical benefits to a large number of patients with advanced cancer. This great and long-awaited success for the immunotherapy of cancer has infused considerable enthusiasm in the field of oncology and fostered the development of combinatorial strategies to target the multiple mechanisms of tumor-induced T-cell dysfunction. Here, we review the critical immunoregulatory mechanisms driving T-cell exhaustion in the TME. We also discuss the development of promising combinatorial immunotherapies to counteract the mechanisms of tumor-induced T-cell dysfunction to improve the clinical efficacy of current immune checkpoint blockades. As our understanding of the mechanisms supporting tumor-induced T-cell dysfunction improves based upon preclinical and clinical studies, we expect that novel combinatorial immunotherapies will emerge to improve the clinical outcome of patients with advanced cancers.

Indexed as

AnimalsAntibodies, MonoclonalAntigen-Presenting CellsAntineoplastic AgentsCostimulatory and Inhibitory T-Cell ReceptorsCTLA-4 AntigenCytokinesEpigenesis, GeneticGene Expression RegulationHumansImmunologic FactorsImmunomodulationMolecular Targeted TherapyMyeloid CellsNeoplasmsProgrammed Cell Death 1 ReceptorAntibodies, MonoclonalAntineoplastic AgentsCostimulatory and Inhibitory T-Cell ReceptorsCTLA-4 AntigenCytokinesImmunologic FactorsProgrammed Cell Death 1 Receptor

Identifiers

PMID27084739
PMCPMC4872712
OpenAlexW2336635113

What OpenQuestion holds

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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.