title: Charting Immune Signaling Proteomes En Route to New Therapeutic Strategies.
abstract: The activation state of an antitumor effector T cell in a tumor depends on the sum of all stimulatory signals and inhibitory signals that it receives in the tumor microenvironment. Accumulating data address the increasing complexity of these signals produced by a myriad of immune checkpoint molecules, cytokines, and metabolites. While reductionist experiments have identified key molecules and their importance in signaling, less clear is the integration of all these signals that allows T cells to guide their responses in health and in disease. Mass spectrometry-based proteomics is well poised to offer such insights, including monitoring emergence of resistance mechanisms to immunotherapeutics during treatments. A major application of this technology is in the discovery and characterization of small-molecule agents capable of enhancing the response to immunotherapeutic agents. Such an approach would reinvigorate small-molecule drug development aimed not at tumor cells but rather at tumor-resident T cells capable of producing dramatic and durable antitumor responses.
authors.affiliation: Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. eric.haura@moffitt.org.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Haura
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Amer A
authors.initials: AA
authors.lastname: Beg
authors.affiliation: Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Uwe
authors.initials: U
authors.lastname: Rix
authors.affiliation: Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
mesh_terms: D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D013058:Mass Spectrometry; D009369:Neoplasms / Q000628:therapy*; D040901:Proteomics; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines