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Nat Chem Biol. 2017 Jun;13(6):681-690. doi: 10.1038/nchembio.2360. Epub 2017 Apr 24.

Global survey of the immunomodulatory potential of common drugs.

Author information

1
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
2
Structural Genomics Consortium, University of Oxford, Oxford, UK and Target Discovery Institute, University of Oxford, Oxford, UK.
3
Christian Doppler Laboratory for Chemical Epigenetics and Anti-infectives, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
4
Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
5
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
6
Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.

Abstract

Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ∼10% of the agents tested affected these cell-cell interactions differentially. The results accurately recapitulated known immunomodulatory drug classes and revealed several clinically approved drugs that unexpectedly harbor the ability to modulate the immune system, which could potentially contribute to their physiological mechanism of action. For instance, the kinase inhibitor crizotinib promoted T cell interactions with monocytes, as well as with cancer cells, through inhibition of the receptor tyrosine kinase MSTR1 and subsequent upregulation of the expression of major histocompatibility complex molecules. The approach offers an attractive platform for the personalized identification and characterization of immunomodulatory therapeutics.

Comment in

PMID:
28437395
PMCID:
PMC5438060
DOI:
10.1038/nchembio.2360
[Indexed for MEDLINE]
Free PMC Article

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