T Cell Signaling Networks in Health and Disease

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Background

Signaling networks control every aspect of T cell biology. Proper signaling promotes T cell development, cellular differentiation, adaptive immune responses and maintenance of immune homeostasis. T cell signaling and activation mechanisms play a fundamental role in disease processes. Dysregulation of signaling via genetic mutations to T cell receptor proximal signaling proteins potentiates multiple clinical pathologies. In many disease contexts including cancer, T cells become dysregulated via chronic signaling and strategies to reactivate tumor specific T cells could be a promising therapeutic route.

The development of chimeric antigen receptor modified T cells (CAR-T) to thwart diseases has tremendous potential but there is likely still an opportunity to better engineer CAR signaling domains for more efficacious therapies. While much is known about signaling mechanisms in T cells, the ability to manipulate and engineer signaling pathways to control T cell activity is still evolving. New technologies have revolutionized our ability to better visualize the organization of signaling processes, characterize signaling cascades at the systems level and study the role of metabolites and signaling lipids in regulating T cell activation. We believe that there is still much to learn about signaling in T cells and that a more in-depth basic understanding of signaling mechanisms could be leveraged to control T cell activity and rationally engineer T cell-based immunotherapies.

This Research Topic aims to solicit studies that elucidate new signaling mechanisms in T cells, connect T cell signaling dysfunction to disease states and engineer signaling networks for T cell-based therapeutics. We will focus on novel research that explores the following areas:

- The role of kinase signaling networks in T cell activation, function and disease

- The function of lipid dependent regulation of signaling networks in T cell biology and potential impact on human disease

- Impact of mutations in T cell signaling molecules in human disease

- Engineering approaches to improve T cell-based therapeutics

Keywords: T cell, T-cell receptor (TCR), Signal transduction, second messengers, chimeric antigen receptor modified T cells (CAR-T), immunotherapy, adaptive immunity

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