Only a minority of patients respond positively to cancer immunotherapy, and addressing this variability is an active area of immunotherapy research. Infiltration of tumors by immune cells is one of the most significant prognostic indicators of response and disease-free survival. However, the ability to noninvasively sample the tumor microenvironment for immune cells remains limited. Imaging in the near-infrared-II region using rare-earth nanocrystals is emerging as a powerful imaging tool for high-resolution deep-tissue imaging. In this paper, we demonstrate that these nanoparticles can be used for noninvasive in vivo imaging of tumor-infiltrating T-cells in a highly aggressive melanoma tumor model. We present nanoparticle synthesis and surface modification strategies for the generation of small, ultrabright, and biocompatible rare-earth nanocrystals necessary for deep tissue imaging of rare cell types. The ability to noninvasively monitor the immune contexture of a tumor during immunotherapy could lead to early identification of nonresponding patients in real time, leading to earlier interventions and better outcomes.
Keywords: Rare-earth nanoparticles; T-cell tracking; biofunctionalization; immunotherapy; melanoma; noninvasive imaging.