Induction of Tertiary Lymphoid Structures With Antitumor Function by a Lymph Node-Derived Stromal Cell Line

Genyuan Zhu; Satoshi Nemoto; Adam W. Mailloux; Patricio Perez-Villarroel; Ryosuke Nakagawa; Rana Falahat; Anders E. Berglund; James J. Mule

doi:10.3389/fimmu.2018.01609

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Induction of Tertiary Lymphoid Structures With Antitumor Function by a Lymph Node-Derived Stromal Cell Line

Journal article

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Induction of Tertiary Lymphoid Structures With Antitumor Function by a Lymph Node-Derived Stromal Cell Line

Genyuan Zhu, Satoshi Nemoto, Adam W. Mailloux, Patricio Perez-Villarroel, Ryosuke Nakagawa, Rana Falahat, Anders E. Berglund and James J. Mule

Frontiers in immunology, Vol.9, pp.1609-1609

07/16/2018

DOI: 10.3389/fimmu.2018.01609

PMCID: PMC6054958

PMID: 30061886

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Abstract

Tertiary lymphoid structures (TLSs) associate with better prognosis in certain cancer types, but their underlying formation and immunological benefit remain to be determined. We established a mouse model of TLSs to study their contribution to antitumor immunity. Because the stroma in lymph nodes (sLN) participates in architectural support, lymphogenesis, and lymphocyte recruitment, we hypothesized that TLSs can be created by sLN. We selected a sLN line with fibroblast morphology that expressed sLN surface markers and lymphoid chemokines. The subcutaneous injection of the sLN line successfully induced TLSs that attracted infiltration of host immune cell subsets. Injection of MC38 tumor lysate-pulsed dendritic cells activated TLS-residing lymphocytes to demonstrate specific cytotoxicity. The presence of TLSs suppressed MC38 tumor growth in vivo by improving antitumor activity of tumor-infiltrating lymphocytes with downregulated immune checkpoint proteins (PD-1 and Tim-3). Future engineering of sLN lines may allow for further enhancements of TLS functions and immune cell compositions.

Immunology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Induction of Tertiary Lymphoid Structures With Antitumor Function by a Lymph Node-Derived Stromal Cell Line
Creators: Genyuan Zhu - Moffitt Cancer Center
Satoshi Nemoto - Moffitt Cancer Center
Adam W. Mailloux - Moffitt Cancer Center
Patricio Perez-Villarroel - Moffitt Cancer Center
Ryosuke Nakagawa - Moffitt Cancer Center
Rana Falahat - Moffitt Cancer Center
Anders E. Berglund - Moffitt Cancer Center
James J. Mule - Moffitt Cancer Center
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.9, pp.1609-1609
DOI: 10.3389/fimmu.2018.01609
PMID: 30061886
PMCID: PMC6054958
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Publisher: Frontiers Media Sa
Number of pages: 10
Grant note: 1R01 CA148995; 1R01 CA184845; P30 CA076292; P50 CA168536 / NCI-NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Dr. Miriam and Sheldon G. Adelson Medical Research Foundation Analytic Microscopy Core at the H. Lee Moffitt Cancer Center & Research Institute P50CA168536 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Cindy and Jon Gruden Fund Chris Sullivan Fund Flow Cytometry Core at the H. Lee Moffitt Cancer Center & Research Institute V Foundation Molecular Genomics Core at the H. Lee Moffitt Cancer Center & Research Institute
Language: English
Date published: 07/16/2018
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297332602771

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