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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 Aug 1

PMID 30061886

Citations 36

Authors

Genyuan Zhu

Satoshi Nemoto

Adam W Mailloux

Patricio Perez-Villarroel

Ryosuke Nakagawa

Rana Falahat

Anders E Berglund

James J Mule

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Artificial Tertiary Lymphoid Structures: Exploring Mesenchymal Stromal Cells as a Platform for Immune Niche Formation.

Zubkova E, Kalinin A, Beloglazova I, Kurilina E, Menshikov M, Parfyonova Y Int J Mol Sci. 2025; 25(24.

PMID: 39769051 PMC: 11676966. DOI: 10.3390/ijms252413286.

Tertiary lymphoid structures in ovarian cancer.

Sun G, Liu Y Front Immunol. 2024; 15:1465516.

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Research trends, hotspots and future directions of tertiary lymphoid structures in cancer: a comprehensive informatics analysis and visualization study.

Yu C, Xu J, Xu S, Tang L, Han Q, Sun Z Discov Oncol. 2024; 15(1):665.

PMID: 39549226 PMC: 11569082. DOI: 10.1007/s12672-024-01556-2.

Tertiary Lymphoid Structures in Microorganism-Related Cancer.

Deng S, Yang X, He L, Hou Y, Meng H Cancers (Basel). 2024; 16(20).

PMID: 39456558 PMC: 11505735. DOI: 10.3390/cancers16203464.

Spatial multiplexed immunofluorescence analysis reveals coordinated cellular networks associated with overall survival in metastatic osteosarcoma.

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