Evidence map›Paper›PMID 25797516›Full record

ReviewTrends in immunology2015

Overcoming T cell exhaustion in infection and cancer.

Kristen E Pauken, E John Wherry

Registry-linked trialOpen access · greenAbstract readReview
In one paragraph

Review in Trends in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04262687 (Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate), which is not on this map. Cited by 750 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
750citing papers in PubMed, 3 pooled it
39.7field-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.

NCT04262687 phase2unknown statusnot on this mapstarted 2021, after this paper: background citation

Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study

TypeinterventionalSponsorFederation Francophone de Cancerologie DigestiveRan2021 to 2024Enrolled55ConditionsColorectal Cancer Metastatic, High Immune Infiltrate, Microsatellite StableArmsCapecitabine, Oxaliplatin, Bevacizumab, Pembrolizumab
3 · Its place in the literature

Who cites it

750 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,156 citations in OpenAlex.

  1. Pooled it
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  4. Axicabtagene Ciloleucel in Combination with Atezolizumab in Patients with Refractory Diffuse Large B-Cell Lymphoma: The Phase 1/2 ZUMA-6 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  5. Trial
  6. Overcoming T cell exhaustion and senescence in CAR T cell therapy for solid tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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690 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

2 authors at 1 institution in 1 country.

Kristen E PaukenInstitute for Immunology and Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, USA.
E John WherryInstitute for Immunology and Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, USA. Electronic address: wherry@mail.med.upenn.edu.
University of Pennsylvania · US

Funding

Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1M
P3: Chemokine-Mediated T Cell Trafficking in HIV Transmission and Immune ResponseP01AI112521 · NIAID · HARVARD MEDICAL SCHOOL · PI LUSTER, ANDREW · 2014 to 2018
$9.8M
Cellular and transcriptional control of exhausted CD8 T cells lineage dynamicsR01AI105343 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2014 to 2017
$1.6M
NIAID NIH HHS AI05343NIAID NIH HHS AI082630NIAID NIH HHS AI112521NIAID NIH HHS P01 AI112521NIAID NIH HHS R01 AI105343NIAID NIH HHS U19 AI082630
6 · The paper itself

Abstract

Inhibitors of the Programmed Cell Death 1: Programmed Cell Death 1 ligand 1 (PD-1:PD-L1) pathway, a central regulator of T cell exhaustion, have been recently shown to be effective for treatment of different cancers. However, clinical responses are mixed, highlighting the need to better understand the mechanisms of action of PD-1:PD-L1, the role of this pathway in immunity to different tumors, and the molecular and cellular effects of PD-1 blockade. Here, we review the molecular regulation of T cell exhaustion, placing recent findings on PD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell exhaustion during chronic infection. We discuss the current understanding of the mechanisms involved in reversing T cell exhaustion, and outline critical areas of focus for future research, both basic and clinical.

Indexed as

AnimalsB7-H1 AntigenChronic DiseaseHepatitisHumansNeoplasmsProgrammed Cell Death 1 ReceptorT-LymphocytesB7-H1 AntigenCD274 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 Receptorcancerchronic infectionimmunotherapyPD-1PD-L1T cell exhaustion

Identifiers

PMID25797516
PMCPMC4393798
OpenAlexW2110305039

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.