期刊
NATURE CHEMICAL BIOLOGY
卷 13, 期 6, 页码 681-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.2360
关键词
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资金
- Austrian Academy of Sciences
- ERC
- Austrian Science Fund [F4711-B20]
- Austrian Federal Ministry of Science, Research and Economy
- National Foundation for Research, Technology and Development
- Swedish Cancer Society
- Knut and Alice Wallenberg Foundation
- Torsten and Ragnar Soderberg Foundation
- Swiss National Science Foundation [P300P3_147897, PP00P3_163961, P2EZP3_159114]
- EMBO [1543-2012]
- Marie-Sklodowska Curie Action Fellowship (SLIM)
- Swiss National Science Foundation (SNF) [P2EZP3_159114, P300P3_147897, PP00P3_163961] Funding Source: Swiss National Science Foundation (SNF)
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, similar to 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.
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