Global survey of the immunomodulatory potential of common drugs.

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. Surprisingly, some 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, potentially contributing 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 MST1R/RON (macrophage-stimulating protein receptor) and subsequent upregulation of MHC (major histocompatibility complex) expression. The approach offers an attractive platform for the personalized identification and characterization of immunomodulatory therapeutics

Using Drosophila models and tools to understand the mechanisms of novel human cancer driver gene function

The formation, overgrowth and metastasis of tumors comprise a complex series of cellular and molecular events resulting from the combined effects of a variety of aberrant signaling pathways, mutations, and epigenetic alterations. Modeling this complexity in vivo requires multiple genes to be manipulated simultaneously, which is technically challenging. Here, we analyze how Drosophila research can further contribute to identifying pathways and elucidating mechanisms underlying novel cancer driver (risk) genes associated with tumor growth and metastasis in humans.Work in the authors laboratory is supported by the Spanish Ministry of Economy and Competitiveness and co-financed by FEDER funds (BFU2015-64239-R, the Spanish State Research Agency, through the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2013-0317), the Scientific Foundation of the Spanish Association Against Cancer (AECC) (CICPF16001DOMÍ), and the Valencian Regional Government’s Prometeo Programme for research groups of excellence (PROMETEO/2017/146) to M.D.Peer reviewe