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

doi:10.1002/advs.202203842

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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 language	English
Article number	2203842
Journal	Advanced Science
Volume	9
Issue number	28
DOIs	https://doi.org/10.1002/advs.202203842
Publication status	Published - 2022 Oct 5

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (No. 2014M3A7B4052192, 2019R1A2C3006587, and 2019R1I1A1A01062020) and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (No. HV22C0009). J.W.L, N.Y.J., P.S., U.P, H.J.R., and H.R.P received a scholarship from the BK21‐plus education program provided by the National Research Foundation of Korea. All illustrations in the figures were created with Biorender.com.

Publisher Copyright:
© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords

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

ASJC Scopus subject areas

Medicine (miscellaneous)
General Chemical Engineering
General Materials Science
Biochemistry, Genetics and Molecular Biology (miscellaneous)
General Engineering
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/advs.202203842

Cite this

Lee, J. W., Park, B. C., Jang, N. Y., Lee, S., Cho, Y. K., Sharma, P., Byun, S. W., Jeon, K., Jeon, Y. H., Park, U., Ro, H. J., Park, H. R., Kim, Y., Lee, D. S., Chung, S., Kim, Y. K., & Cho, N. H. (2022). Inducing Ectopic T Cell Clusters Using Stromal Vascular Fraction Spheroid-Based Immunotherapy to Enhance Anti-Tumor Immunity. Advanced Science, 9(28), Article 2203842. https://doi.org/10.1002/advs.202203842

Lee, JW, Park, BC, Jang, NY, Lee, S, Cho, YK, Sharma, P, Byun, SW, Jeon, K, Jeon, YH, Park, U, Ro, HJ, Park, HR, Kim, Y, Lee, DS, Chung, S , Kim, YK & Cho, NH 2022, 'Inducing Ectopic T Cell Clusters Using Stromal Vascular Fraction Spheroid-Based Immunotherapy to Enhance Anti-Tumor Immunity', Advanced Science, vol. 9, no. 28, 2203842. https://doi.org/10.1002/advs.202203842

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title = "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.",

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

note = "Funding Information: This work was supported by the National Research Foundation of Korea (No. 2014M3A7B4052192, 2019R1A2C3006587, and 2019R1I1A1A01062020) and by a grant from the Korea Health Technology R\&D Project through the Korea Health Industry Development Institute (KHIDI) (No. HV22C0009). J.W.L, N.Y.J., P.S., U.P, H.J.R., and H.R.P received a scholarship from the BK21‐plus education program provided by the National Research Foundation of Korea. All illustrations in the figures were created with Biorender.com. Publisher Copyright: {\textcopyright} 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.",

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AU - Lee, Jae Won

AU - Park, Bum Chul

AU - Jang, Na Yoon

AU - Lee, Sihyeon

AU - Cho, Young Kyu

AU - Sharma, Prashant

AU - Byun, Sang Won

AU - Jeon, Kyeongseok

AU - Jeon, Yun Hui

AU - Park, Uni

AU - Ro, Hyo Jin

AU - Park, Hyo Ree

AU - Kim, Yuri

AU - Lee, Dong Sup

AU - Chung, Seok

AU - Kim, Young Keun

AU - Cho, Nam Hyuk

N1 - Funding Information: This work was supported by the National Research Foundation of Korea (No. 2014M3A7B4052192, 2019R1A2C3006587, and 2019R1I1A1A01062020) and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (No. HV22C0009). J.W.L, N.Y.J., P.S., U.P, H.J.R., and H.R.P received a scholarship from the BK21‐plus education program provided by the National Research Foundation of Korea. All illustrations in the figures were created with Biorender.com. Publisher Copyright: © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

PY - 2022/10/5

Y1 - 2022/10/5

N2 - 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.

AB - 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.

KW - cancer immunotherapy

KW - dendritic cells

KW - immunotherapy

KW - iron-oxide zinc oxide nanoparticles

KW - spheroid

KW - stromal vascular fraction

KW - tertiary lymphoid structure

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DO - 10.1002/advs.202203842

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AN - SCOPUS:85137325890

SN - 2198-3844

VL - 9

JO - Advanced Science

JF - Advanced Science

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M1 - 2203842

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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