Immunosuppressive Strategies for the Prevention or Treatment of Acute GVHD. Panel A shows several classic immunosuppressive approaches that are in routine clinical use. Panel B shows primarily new strategies that have shown efficacy in preclinical models of GVHD, although some have been tested in clinical trials, including the inhibition of Janus kinase (JAK) and rho-associated protein kinase 1 (ROCK-1). The blockade of phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MEK) proteins 1 and 2, aurora A kinase, and cyclin-dependent kinase 2 (CDK2) has been shown to reduce acute GVHD in murine models. The different signaling pathways in which these kinases have a nonredundant function are shown. APC denotes antigen-presenting cell, MLC myosin light chain, mTOR mammalian target of rapamycin, NFAT nuclear factor of activated T cells, STAT signal transducer and activator of transcription, and TNF-R tumor necrosis factor receptor. #Pathophysiology #IM #Honc #Pharm #GVHD #GraftVersusHostDisease #Immunosuppression #NEJM
