Charting Immune Signaling Proteomes En Route to New Therapeutic Strategies

摘要

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, cyto-kines, 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 immunother-apeutics 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.