Evidence map›Paper›PMID 33768207›Full record

ArticleNature cancer2020

Extracellular cGAMP is a cancer cell-produced immunotransmitter involved in radiation-induced anti-cancer immunity.

Jacqueline A Carozza, Volker Böhnert, Khanh C Nguyen, Gemini Skariah, Kelsey E Shaw, Jenifer A Brown, Marjan Rafat, Rie von Eyben, Edward E Graves, Jeffrey S Glenn and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers.

0numbers the graph read from it
0cells of the map it votes in
196citing papers in PubMed
13.2field-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

196 citing papers in PubMed, 324 citations in OpenAlex.

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  13. Extracellular cGAMP in health and disease.Molecular biomedicine · 2026
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136 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

12 authors at 2 institutions in 1 country.

Jacqueline A Carozza *Department of Chemistry, Stanford University, Stanford, CA, USA.
Volker Böhnert *Stanford ChEM-H, Stanford University, Stanford, CA, USA.
Khanh C NguyenDepartments of Medicine and Microbiology & Immunology, Stanford University, School of Medicine, Stanford, CA, USA.
Gemini SkariahStanford ChEM-H, Stanford University, Stanford, CA, USA.
Kelsey E ShawStanford ChEM-H, Stanford University, Stanford, CA, USA.
Jenifer A BrownStanford ChEM-H, Stanford University, Stanford, CA, USA.
Marjan RafatDepartment of Radiation Oncology, Stanford University, School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9444-4379
Rie von EybenDepartment of Radiation Oncology, Stanford University, School of Medicine, Stanford, CA, USA.
Edward E GravesDepartment of Radiation Oncology, Stanford University, School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4265-9041
Jeffrey S GlennDepartments of Medicine and Microbiology & Immunology, Stanford University, School of Medicine, Stanford, CA, USA.
Mark SmithStanford ChEM-H, Stanford University, Stanford, CA, USA.
Lingyin LiStanford ChEM-H, Stanford University, Stanford, CA, USA. lingyinl@stanford.edu.ORCID http://orcid.org/0000-0003-4386-7926
Stanford University · USStanford Medicine · US

Funding

Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
Chemical biology of innate immunity for treating cancer and autoimmunityDP2CA228044 · NCI · STANFORD UNIVERSITY · PI LI, LINGYIN · 2017 to 2017
$2.4M
Radiation-Induced Tumor Cell MigrationR01CA197136 · NCI · STANFORD UNIVERSITY · PI GRAVES, EDWARD E. · 2015 to 2019
$1.9M
Deconstructing the Tumor Microenvironment and its Role in MetastasisR00CA201304 · NCI · VANDERBILT UNIVERSITY · PI RAFAT, MARJAN · 2018 to 2020
$728k
Small Animal Radiation Research Platform @ StanfordS10OD018208 · OD · STANFORD UNIVERSITY · PI GRAVES, EDWARD E. · 2014 to 2014
$600k
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
Deconstructing the Tumor Microenvironment and its Contribution to MetastasisK99CA201304 · NCI · STANFORD UNIVERSITY · PI RAFAT, MARJAN · 2016 to 2017
$199k
Harnessing the innate immunotransmitter cGAMP for anti-cancer therapyF31CA239510 · NCI · STANFORD UNIVERSITY · PI CAROZZA, JACQUELINE · 2019 to 2021
$104k
NCI NIH HHS DP2 CA228044NCI NIH HHS F31 CA239510NCI NIH HHS K99 CA201304NCI NIH HHS R00 CA201304NCI NIH HHS R01 CA197136NCRR NIH HHS S10 RR027431NIAID NIH HHS U19 AI109662NIH HHS S10 OD018208
6 · The paper itself

Abstract

2'3'-cyclic GMP-AMP (cGAMP) is an intracellular second messenger that is synthesized in response to cytosolic double-stranded DNA and activates the innate immune STING pathway. Our previous discovery of its extracellular hydrolase ENPP1 hinted at the existence of extracellular cGAMP. Here, we detected that cGAMP is continuously exported but then efficiently cleared by ENPP1, explaining why it has previously escaped detection. By developing potent, specific, and cell impermeable ENPP1 inhibitors, we found that cancer cells continuously export cGAMP in culture at steady state and at higher levels when treated with ionizing radiation (IR). In mouse tumors, depletion of extracellular cGAMP decreased tumor-associated immune cell infiltration and abolished the curative effect of IR. Boosting extracellular cGAMP with ENPP1 inhibitors synergized with IR to delay tumor growth. In conclusion, extracellular cGAMP is an anti-cancer immunotransmitter that could be harnessed to treat cancers with low immunogenicity.

Indexed as

NeoplasmsNucleotides, CyclicAnimalsMiceSecond Messenger Systemscyclic guanosine monophosphate-adenosine monophosphateNucleotides, Cyclic

Identifiers

PMID33768207
PMCPMC7990037
OpenAlexW3006766295

What OpenQuestion holds

Textmetadata
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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.