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

Jae Won Lee, Bum Chul Park, Na Yoon Jang, Sihyeon Lee, Young Kyu Cho, Prashant Sharma, Sang Won Byun, Kyeongseok Jeon, Yun Hui Jeon, Uni Park, Hyo Jin Ro, Hyo Ree Park, Yuri Kim, Dong Sup Lee, Seok Chung, Young Keun Kim, Nam Hyuk Cho

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number2203842
JournalAdvanced Science
Volume9
Issue number28
DOIs
StatePublished - 5 Oct 2022

Keywords

  • cancer immunotherapy
  • dendritic cells
  • immunotherapy
  • iron-oxide zinc oxide nanoparticles
  • spheroid
  • stromal vascular fraction
  • tertiary lymphoid structure

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