Inducing Ectopic T Cell Clusters Using Stromal Vascular Fraction Spheroid-Based Immunotherapy to Enhance Anti-Tumor Immunity

Abstract

Tertiary lymphoid structures (TLSs) provide specialized niches for immune cells, resulting in improved prognoses for patients undergoing cancer immunotherapy. Shaping TLS-like niches may improve anti-cancer immunity and overcome the current limitations of immune cell-based immunotherapy. Here, it is shown that stromal vascular fraction (SVF) from adipose tissues can enhance dendritic cell (DC)-mediated T cell immunity by inducing ectopic T lymphocyte clusters. SVF cells expanded ex vivo have phenotypes and functions similar to those of fibroblastic reticular cells in a secondary lymphoid organ, and their properties can be modulated using three-dimensional spheroid culture and coculture with DCs spiked with antigen-loaded iron oxide-zinc oxide core-shell nanoparticles. Thereby, the combination of SVF spheroids and mature DCs significantly augments T cell recruitment and retention at the injection site. This strategy elicits enhanced antigen-specific immune response and anti-tumoral immunity in mice, illustrating the potential for a novel immunotherapeutic design using SVF as a structural scaffold for TLS.

Keywords: cancer immunotherapy; dendritic cells; immunotherapy; iron-oxide zinc oxide nanoparticles; spheroid; stromal vascular fraction; tertiary lymphoid structure.