Evidence map›Paper›PMID 33597234›Full record

ArticleScience advances2021

Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion.

Jose M Ayuso, Shujah Rehman, Maria Virumbrales-Munoz, Patrick H McMinn, Peter Geiger, Cate Fitzgerald, Tiffany Heaster, Melissa C Skala, David J Beebe

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
8.6field-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

104 citing papers in PubMed, 153 citations in OpenAlex.

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  19. Cancer metastasisFrontiers in bioengineering and biotechnology · 2026
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44 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

9 authors at 1 institution in 1 country.

Jose M AyusoDepartment of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA. ayusodomingu@wisc.edu mcskala@wisc.edu djbeebe@wisc.edu.ORCID 0000-0002-9414-1845
Shujah RehmanMorgridge Institute for Research, 330 N Orchard Street, Madison, WI, USA.ORCID 0000-0001-9527-743X
Maria Virumbrales-MunozDepartment of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.ORCID 0000-0003-3660-8651
Patrick H McMinnDepartment of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.ORCID 0000-0002-1914-2346
Peter GeigerDepartment of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
Cate FitzgeraldDepartment of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.ORCID 0000-0002-5901-4584
Tiffany HeasterMorgridge Institute for Research, 330 N Orchard Street, Madison, WI, USA.
Melissa C SkalaMorgridge Institute for Research, 330 N Orchard Street, Madison, WI, USA. ayusodomingu@wisc.edu mcskala@wisc.edu djbeebe@wisc.edu.ORCID 0000-0002-6320-7637
David J BeebeDepartment of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA. ayusodomingu@wisc.edu mcskala@wisc.edu djbeebe@wisc.edu.ORCID 0000-0002-0415-9006
University of Wisconsin–Madison · US

Funding

Radiation response within the tumor microenvironmentR01CA164492 · NCI · UNIVERSITY OF CHICAGO · PI KRON, STEPHEN J. · 2011 to 2015
$4.8M
Optical imaging of pancreas cancer organoids for drug development and personalized treatmentR01CA211082 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2017 to 2021
$3.5M
(PQ7) Quantitative in vivo optical imaging of tumor heterogeneityR01CA205101 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2016 to 2020
$1.9M
Cellular-level Optical Metabolic Imaging to Predict Drug Response in CancerR01CA185747 · NCI · VANDERBILT UNIVERSITY · PI SKALA, MELISSA CAROLINE · 2014 to 2019
$1.6M
NCI NIH HHS R01 CA164492NCI NIH HHS R01 CA185747NCI NIH HHS R01 CA205101NCI NIH HHS R01 CA211082
6 · The paper itself

Abstract

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus, here, we used an in vitro microfluidic tumor-on-a-chip platform to evaluate how NK cells respond to the tumor-induced suppressive environment. The results demonstrated that the suppressive environment created by the tumor gradually eroded NK cell cytotoxic capacity, leading to compromised NK cell surveillance and tumor tolerance. Further, NK cell exhaustion persisted for an extended period of time after removing NK cells from the microfluidic platform. Last, the addition of checkpoint inhibitors and immunomodulatory agents alleviated NK cell exhaustion.

Indexed as

Antineoplastic AgentsNeoplasmsHumansKiller Cells, NaturalLab-On-A-Chip DevicesMicrofluidicsAntineoplastic Agents

Identifiers

PMID33597234
PMCPMC7888951
OpenAlexW3132584473

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.