Evidence map›Paper›PMID 30420753›Full record

ArticleNature medicine2019

Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade.

Ziming Wang, Ethan G Aguilar, Jesus I Luna, Cordelia Dunai, Lam T Khuat, Catherine T Le, Annie Mirsoian, Christine M Minnar, Kevin M Stoffel, Ian R Sturgill and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 599 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
599citing papers in PubMed, 6 pooled it
47.5field-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

599 citing papers in PubMed, 6 syntheses or guidelines pooled it, 823 citations in OpenAlex.

  1. Pooled it
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  6. Pooled it
  7. Article
  8. Article
  9. Obesity Promotes Lung Carcinogenesis Through Airway Immune Dysfunction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
    Article
  10. Review
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  18. Coixenolide Enhances Antitumor Immunity of Cytotoxic CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  19. Article
  20. Observational

539 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 11 institutions in 1 country.

Ziming Wang *Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Ethan G Aguilar *Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Jesus I LunaDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Cordelia DunaiDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.ORCID http://orcid.org/0000-0001-5799-2387
Lam T KhuatDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Catherine T LeDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Annie MirsoianDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Christine M MinnarDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Kevin M StoffelDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Ian R SturgillDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Steven K GrossenbacherDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Sita S WithersDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Robert B RebhunDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.ORCID http://orcid.org/0000-0002-8047-3494
Dennis J Hartigan-O'ConnorDivision of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Gema Méndez-LagaresDepartment of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA.
Alice F TarantalCalifornia National Primate Research Center, University of California Davis, Davis, CA, USA.
R Rivkah IsseroffDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Thomas S GriffithDepartment of Urology, Center for Immunology, Masonic Cancer Center, Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN, USA.
Kurt A SchalperDepartment of Pathology & Translational Immuno-oncology Laboratory, Yale University School of Medicine, New Haven, CT, USA.
Alexander MerleevDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Asim SahaMasonic Cancer Center and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Emanual MaverakisDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Karen KellyDepartment of Internal Medicine, Division of Hematology and Oncology, University of California Davis Schoolof Medicine, Sacramento, CA, USA.
Raid AljumailyDepartment of Internal Medicine, Section of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Sami IbrahimiDepartment of Internal Medicine, Section of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Sarbajit MukherjeeDepartment of Internal Medicine, Section of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Michael MachiorlattiDepartment of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Sara K VeselyDepartment of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Dan L LongoLaboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, MD, USA.
Bruce R BlazarMasonic Cancer Center and Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Robert J CanterDivision of Surgical Oncology, Department of Surgery, University of California Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA.
William J MurphyDepartment of Dermatology, University of California Davis School of Medicine, Sacramento, CA, USA. wmjmurphy@ucdavis.edu.ORCID http://orcid.org/0000-0002-2793-401X
Arta M MonjazebDepartment of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Universityof California School of Medicine, Sacramento, CA, USA.
University of California, Davis · USUniversity of Oklahoma Health Sciences Center · USUC Davis Comprehensive Cancer CenterUniversity of Minnesota Medical Center · USNational Institute on Aging · USSacramento VA Medical Center · USUniversity of California Davis Medical Center · USUniversity of California, San Francisco · USUniversity of California System · USUniversity of Minnesota · USYale University · US

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI J SUNIL RAO · 1995 to 2026
$48.2M
Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Wade Williams · 2018 to 2026
$27.1M
TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood DiseasesR24HL085794 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI TARANTAL, ALICE F · 2006 to 2016
$9.7M
Enhancing Treg Therapeutic Efficacy in GVHDR01HL118979 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, HIPPEN, KELI L · 2014 to 2025
$6.7M
T-CELL TARGETING FOR GVHDR01HL056067 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1995 to 2022
$5.4M
In Vivo Prevention of Murine GVHDR37AI034495 · NIAID · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar · 2017 to 2026
$5.4M
Mouse Metabolic Phenotyping Center (MMPC) at UC DavisU24DK092993 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2011 to 2015
$4.1M
IT by CD40 stimulation and IL2 against renal cell carcinR01CA095572 · NCI · UNIVERSITY OF NEVADA RENO · PI MURPHY, WILLIAM JOSEPH · 2002 to 2017
$4.0M
Multispecies Comparison of the Impact of Obesity on GVHD/GVTR01CA214048 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MURPHY, WILLIAM JOSEPH · 2017 to 2021
$3.2M
NCI NIH HHS P01 CA065493NCI NIH HHS P30 CA093373NCI NIH HHS P30 CA225520NCI NIH HHS R01 CA095572NCI NIH HHS R01 CA195904NCI NIH HHS R01 CA214048NCI NIH HHS T32 CA009138NHLBI NIH HHS R01 HL056067NHLBI NIH HHS R01 HL118979NHLBI NIH HHS R24 HL085794NIAID NIH HHS R37 AI034495NIDDK NIH HHS U24 DK092993NIH HHS P51 OD011107NIH HHS S10 OD018223
6 · The paper itself

Abstract

The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors impacting outcome. Obesity is reaching pandemic proportions and is a major risk factor for certain malignancies, but the impact of obesity on immune responses, in general and in cancer immunotherapy, is poorly understood. Here, we demonstrate, across multiple species and tumor models, that obesity results in increased immune aging, tumor progression and PD-1-mediated T cell dysfunction which is driven, at least in part, by leptin. However, obesity is also associated with increased efficacy of PD-1/PD-L1 blockade in both tumor-bearing mice and clinical cancer patients. These findings advance our understanding of obesity-induced immune dysfunction and its consequences in cancer and highlight obesity as a biomarker for some cancer immunotherapies. These data indicate a paradoxical impact of obesity on cancer. There is heightened immune dysfunction and tumor progression but also greater anti-tumor efficacy and survival after checkpoint blockade which directly targets some of the pathways activated in obesity.

Indexed as

Disease ProgressionAdultAnimalsBody WeightCell Line, TumorCell ProliferationDietFemaleHumansImmunotherapyLeptinMaleMice, Inbred C57BLMice, ObeseMiddle AgedNeoplasmsLeptinProgrammed Cell Death 1 Receptor

Identifiers

PMID30420753
PMCPMC6324991
OpenAlexW2898946138

What OpenQuestion holds

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Registered trials

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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.