Abstract
Immunotherapy drugs are transforming the clinical care landscape of major human diseases from cancer, to inflammatory diseases, cardiovascular diseases, neurodegenerative diseases and even aging. In polygenic immune-mediated inflammatory diseases (IMIDs), the clinical benefits of immunotherapy have nevertheless remained limited to a subset of patients. Yet the identification of new actionable molecular candidates has remained challenging, and the use of standard of care imaging and/or histological diagnostic assays has failed to stratify potential responders from non-responders to biotherapies already available. We argue that these limitations partly stem from a poor understanding of disease pathophysiology and insufficient characterization of the roles assumed by candidate targets during disease initiation, progression and treatment. By transforming the resolution and scale of tissue cell mapping, high-resolution profiling strategies offer unprecedented opportunities to the understanding of immunopathogenic events in human IMID lesions. Here we discuss the potential for single-cell technologies to reveal relevant pathogenic cellular programs in IMIDs and to enhance patient stratification to guide biotherapy eligibility and clinical trial design.