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

被引：12

作者：

Lee, Jae-Won ^{[1
,2
,3
]}

Park, Bum Chul ^{[4
,5
]}

Jang, Na Yoon ^{[1
,2
]}

Lee, Sihyeon ^{[1
,2
]}

Cho, Young Kyu ^{[6
]}

Sharma, Prashant ^{[1
,2
]}

Byun, Sang Won ^{[4
]}

Jeon, Kyeongseok ^{[1
,2
]}

Jeon, Yun-Hui ^{[1
]}

Park, Uni ^{[1
,2
]}

Ro, Hyo Jin ^{[1
,2
]}

Park, Hyo Ree ^{[1
,2
]}

Kim, Yuri ^{[1
,2
,3
]}

Lee, Dong-Sup ^{[1
]}

Chung, Seok ^{[6
]}

Kim, Young Keun ^{[4
,5
]}

Cho, Nam-Hyuk ^{[1
,2
,3
,7
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea

[2] Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul 03080, South Korea

[3] Seoul Natl Univ, Coll Med, Inst Endem Dis, Seoul 03080, South Korea

[4] Korea Univ, Dept Mat Sci & Engn, Seoul 02481, South Korea

[5] Korea Univ, Brain Korea Ctr Smart Mat & Devices, Seoul 02841, South Korea

[6] Korea Univ, Sch Mech Engn, Seoul 02841, South Korea

[7] Seoul Natl Univ, Bundang Hosp, Seongnam Si 13620, Gyeonggi Do, South Korea

来源：

ADVANCED SCIENCE | 2022年 / 9卷 / 28期

基金：

新加坡国家研究基金会;

关键词：

cancer immunotherapy; dendritic cells; immunotherapy; iron-oxide zinc oxide nanoparticles; spheroid; stromal vascular fraction; tertiary lymphoid structure; FIBROBLASTIC RETICULAR CELLS; LYMPH-NODES; DENDRITIC CELLS; RECEPTOR; DIFFERENTIATION; HOMEOSTASIS; MATURATION; SURVIVAL;

D O I：

10.1002/advs.202203842

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：13

共 45 条

[1] Dendritic cells in remodeling of lymph nodes during immune responses [J].

Acton, Sophie E. ;

Reis e Sousa, Caetano .

IMMUNOLOGICAL REVIEWS, 2016, 271 (01) :221-229

[2] Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2 [J].

Acton, Sophie E. ;

Astarita, Jillian L. ;

Malhotra, Deepali ;

Lukacs-Kornek, Veronika ;

Franz, Bettina ;

Hess, Paul R. ;

Jakus, Zoltan ;

Kuligowski, Michael ;

Fletcher, Anne L. ;

Elpek, Kutlu G. ;

Bellemare-Pelletier, Angelique ;

Sceats, Lindsay ;

Reynoso, Erika D. ;

Gonzalez, Santiago F. ;

Graham, Daniel B. ;

Chang, Jonathan ;

Peters, Anneli ;

Woodruff, Matthew ;

Kim, Young-A. ;

Swat, Wojciech ;

Morita, Takashi ;

Kuchroo, Vijay ;

Carroll, Michael C. ;

Kahn, Mark L. ;

Wucherpfennig, Kai W. ;

Turley, Shannon J. .

IMMUNITY, 2012, 37 (02) :276-289

[3] A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function [J].

Anderson, DM ;

Maraskovsky, E ;

Billingsley, WL ;

Dougall, WC ;

Tometsko, ME ;

Roux, ER ;

Teepe, MC ;

DuBose, RF ;

Cosman, D ;

Galibert, L .

NATURE, 1997, 390 (6656) :175-179

[4] Inducible Tertiary Lymphoid Structures: Promise and Challenges for Translating a New Class of Immunotherapy [J].

Aoyama, Shota ;

Nakagawa, Ryosuke ;

Mule, James J. ;

Mailloux, Adam W. .

FRONTIERS IN IMMUNOLOGY, 2021, 12

[5] Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic inflammation [J].

Barone, Francesca ;

Gardner, David H. ;

Nayar, Saba ;

Steinthal, Nathalie ;

Buckley, Christopher D. ;

Luther, Sanjiv A. .

FRONTIERS IN IMMUNOLOGY, 2016, 7

[6] Inflammation-induced formation of fat-associated lymphoid clusters [J].

Benezech, Cecile ;

Luu, Nguyet-Thin ;

Walker, Jennifer A. ;

Kruglov, Andrei A. ;

Loo, Yunhua ;

Nakamura, Kyoko ;

Zhang, Yang ;

Nayar, Saba ;

Jones, Lucy H. ;

Flores-Langarica, Adriana ;

McIntosh, Alistair ;

Marshall, Jennifer ;

Barone, Francesca ;

Besra, Gurdyal ;

Miles, Katherine ;

Allen, Judith E. ;

Gray, Mohini ;

Kollias, George ;

Cunningham, Adam F. ;

Withers, David R. ;

Toellner, Kai Michael ;

Jones, Nick D. ;

Veldhoen, Marc ;

Nedospasov, Sergei A. ;

McKenzie, Andrew N. J. ;

Caamano, Jorge H. .

NATURE IMMUNOLOGY, 2015, 16 (08) :819-+

[7] Lymphotoxin-β Receptor Signaling through NF-κB2-RelB Pathway Reprograms Adipocyte Precursors as Lymph Node Stromal Cells [J].

Benezech, Cecile ;

Mader, Emma ;

Desanti, Guillaume ;

Khan, Mahmood ;

Nakamura, Kyoko ;

White, Andrea ;

Ware, Carl F. ;

Anderson, Graham ;

Caamano, Jorge H. .

IMMUNITY, 2012, 37 (04) :721-734

[8] Dendritic Cell-Based Immunotherapy: State of the Art and Beyond [J].

Bol, Kalijn F. ;

Schreibelt, Gerty ;

Gerritsen, Winald R. ;

de Vries, I. Jolanda M. ;

Figdor, Carl G. .

CLINICAL CANCER RESEARCH, 2016, 22 (08) :1897-1906

[9] Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling [J].

Brown, Flavian D. ;

Sen, Debattama R. ;

LaFleur, Martin W. ;

Godec, Jernej ;

Lukacs-Kornek, Veronika ;

Schildberg, Frank A. ;

Kim, Hye-Jung ;

Yates, Kathleen B. ;

Ricoult, Stephane J. H. ;

Bi, Kevin ;

Trombley, Justin D. ;

Kapoor, Varun N. ;

Stanley, Illana A. ;

Cremasco, Viviana ;

Danial, Nika N. ;

Manning, Brendan D. ;

Sharpe, Arlene H. ;

Haining, W. Nicholas ;

Turley, Shannon J. .

NATURE IMMUNOLOGY, 2019, 20 (12) :1668-+

[10] A short field guide to fibroblast function in immunity [J].

Buechler, Matthew B. ;

Turley, Shannon J. .

SEMINARS IN IMMUNOLOGY, 2018, 35 (0C) :48-58

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