title: Signaling in Effector Lymphocytes: Insights toward Safer Immunotherapy.
abstract: Receptors on T and NK cells systematically propagate highly complex signaling cascades that direct immune effector functions, leading to protective immunity. While extensive studies have delineated hundreds of signaling events that take place upon receptor engagement, the precise molecular mechanism that differentially regulates the induction or repression of a unique effector function is yet to be fully defined. Such knowledge can potentiate the tailoring of signal transductions and transform cancer immunotherapies. Targeted manipulations of signaling cascades can augment one effector function such as antitumor cytotoxicity while contain the overt generation of pro-inflammatory cytokines that contribute to treatment-related toxicity such as "cytokine storm" and "cytokine-release syndrome" or lead to autoimmune diseases. Here, we summarize how individual signaling molecules or nodes may be optimally targeted to permit selective ablation of toxic immune side effects.
authors.affiliation: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute , Milwaukee, WI , USA.
authors.forename: Kamalakannan
authors.initials: K
authors.lastname: Rajasekaran
authors.affiliation: Laboratory of Lymphocyte Biology, Blood Research Institute, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Riese
authors.affiliation: Laboratory of Stem Cell Transcriptional Regulation, Blood Research Institute, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Medicine, Medical College of Wisconsin , Milwaukee, WI , USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Monica S
authors.initials: MS
authors.lastname: Thakar
authors.affiliation: Department of Microbiology and Immunology, Center for Synthetic Immunity at the Geisel School of Medicine at Dartmouth , Lebanon, NH , USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sentman
authors.affiliation: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Milwaukee, WI, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Malarkannan
keywords: NK and T cells; NKG2D; immunotherapy; signaling; target molecules