A Fluorescence-Afterglow Reporter for In Vivo Differentiation of Three Tumor Immunophenotypes

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunology

Background:

• Cancer immunotherapy success depends on tumor immunophenotype (inflamed, immune-excluded, immune-desert).
• Noninvasive methods to differentiate these phenotypes and predict treatment outcomes are lacking.

Purpose of the Study:

• To develop a real-time, in vivo reporter for differentiating tumor immunophenotypes.
• To assess the reporter's ability to predict immunotherapy efficacy.

Main Methods:

• Developed a fluorescence-afterglow reporter (FAR) with dual-signal logic.
• FAR simultaneously reports M1 macrophage polarization (nitric oxide-responsive NIRF) and tumor cell apoptosis (Caspase-3-activatable afterglow).
• Differentiated inflamed, immune-excluded, and immune-desert phenotypes in mice and monitored therapeutic conversion.

Main Results:

• FAR accurately differentiated the three tumor immunophenotypes in vivo.
• The reporter successfully monitored the conversion of immune-excluded to inflamed tumors after combination therapy.
• FAR signal patterns correlated with therapeutic outcomes, offering early predictive value for immunotherapy efficacy.

Conclusions:

• FAR provides functional insights into the tumor immune microenvironment.
• This dual-signal reporter is a powerful tool for guiding personalized cancer immunotherapy.
• FAR enables noninvasive differentiation of tumor immunophenotypes for predicting treatment response.