Evidence map›Paper›PMID 24711415›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies.

Oliver M T Pearce, Heinz Läubli, Andrea Verhagen, Patrick Secrest, Jiquan Zhang, Nissi M Varki, Paul R Crocker, Jack D Bui, Ajit Varki

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 73 citations in OpenAlex.

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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 2 institutions in 2 countries.

Oliver M T PearceDepartments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
Heinz Läubli
Andrea Verhagen
Patrick Secrest
Jiquan Zhang
Nissi M Varki
Paul R Crocker
Jack D Bui
Ajit Varki
University of Dundee · GBUniversity of California, San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
SULFATED OLIGOSACCHARIDES OF NORMAL AND MALIGNANT CELLSR01CA038701 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, AJIT P · 1985 to 2015
$5.5M
NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA038701NCI NIH HHS R01CA38701
6 · The paper itself

Abstract

Compelling evidence for naturally occurring immunosurveillance against malignancies informs and justifies some current approaches toward cancer immunotherapy. However, some types of immune reactions have also been shown to facilitate tumor progression. For example, our previous studies showed that although experimental tumor growth is enhanced by low levels of circulating antibodies directed against the nonhuman sialic acid N-glycolyl-neuraminic acid (Neu5Gc), which accumulates in human tumors, growth could be inhibited by anti-Neu5Gc antibodies from a different source, in a different model. However, it remains generally unclear whether the immune responses that mediate cancer immunosurveillance vs. those responsible for inflammatory facilitation are qualitatively and/or quantitatively distinct. Here, we address this question using multiple murine tumor growth models in which polyclonal antibodies against tumor antigens, such as Neu5Gc, can alter tumor progression. We found that although growth was stimulated at low antibody doses, it was inhibited by high doses, over a linear and remarkably narrow range, defining an immune response curve (IRC; i.e., inverse hormesis). Moreover, modulation of immune responses against the tumor by altering antibody avidity or by enhancing innate immunity shifted the IRC in the appropriate direction. Thus, the dualistic role of immunosurveillance vs. inflammation in modulating tumor progression can be quantitatively distinguished in multiple model systems, and can occur over a remarkably narrow range. Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer.

Indexed as

Adaptive ImmunityAnimalsAntibodies, MonoclonalAntibodies, NeoplasmAntibody AffinityBurkitt LymphomaCell Line, TumorCell ProliferationDisease Models, AnimalDisease ProgressionHormesisHumansImmunoglobulin GInflammationKiller Cells, NaturalMacrophagesAntibodies, MonoclonalAntibodies, NeoplasmImmunoglobulin GNeuraminic AcidsN-glycolylneuraminic acidSialic Acid Binding Immunoglobulin-like Lectinsantibody-dependent cellular cytotoxicityM2 polarizationNK cellstumor-associated macrophages

Identifiers

PMID24711415
PMCPMC4000847
OpenAlexW2003559649

What OpenQuestion holds

Textmetadata
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.