Nat. Biotechnol. (2019)

Biomarkers have great potential for the early detection of disease but can suffer drawbacks in their sensitivity and specificity. In Nature Biotechnology, Gambhir and colleagues exploit the functional plasticity and tumor-homing ability of macrophages to engineer a cellular reporter that can diagnose the presence of cancer in a highly sensitive way. Within the tumor microenvironment, macrophages reliably switch to an ‘M2-like’ phenotype characterized most clearly by their expression of arginase-1. Macrophages engineered to express and release Gaussia luciferase after upregulation of arginase-1 can report the presence of even very small tumors (< 50 mm3), including those that are below the detection limits of positron-emission tomography scanning. Reporter activity occurs only in an anti-inflammatory tumor microenvironment. This cellular reporter approach might be applicable for the diagnosis of variety of disease states.