Unlocking the Full Potential of Immunotherapy: Visualizing and Remodeling the Tumor Immune Microenvironment With Aggregation-Induced Emission Luminogens

Abstract

The tumor immune microenvironment (TIME) orchestrates a dynamic network of malignant, immune, and stromal cells, profoundly influencing cancer progression and therapeutic outcomes. Despite the transformative impact of immunotherapies, their efficacy remains limited by the immunosuppressive and heterogeneous nature of TIME. Overcoming these barriers requires platforms can both precisely visualizing immune–tumor interactions and actively modulating the local immune landscape. Aggregation-induced emission luminogens (AIEgens), proposed over two decades ago, have emerged as versatile and powerful tools that feature strong brightness in physiological environments and facile modulation of energy dissipation for phototherapy, enabling real-time monitoring of immune dynamics and induction of immunogenic responses. Herein, we summarize recent advances in AIEgen-based platforms for immunotherapy, with a particular emphasis on the emerging potential of AIEgens in immunotherapy, followed by rational design strategies for tailoring photophysical properties, high-fidelity mapping of immune–tumor interactions, and synergistic therapeutic modalities to reprogram the TIME. We further discuss the critical limitations that impede their clinical translation and outline future opportunities to accelerate their deployment in precision oncology. By positioning AIEgens systems at the interface of materials science and immunology, this review highlights their capacity to actively modulate the TIME and offers a framework to guide the design of next-generation precision immunotherapies.

Keywords

aggregation-induced emission / fluorescence imaging / immunotherapy / phototherapy / tumor immune microenvironment

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