Simultaneous STING and lymphotoxin-β receptor activation induces B cell responses in tertiary lymphoid structures to potentiate antitumor immunity Article Swipe
Junko Sawada
,
Yuzo Kikuchi
,
Maxwell Duah
,
José Luís Herrera
,
Fumiaki Kanamori
,
Krisztián Csomós
,
Tomoko Stansel
,
Nobuyoshi Hiraoka
,
Masayuki Yoshida
,
Jolán E. Walter
,
Carl F. Ware
,
Masanobu Komatsu
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41590-025-02259-8
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41590-025-02259-8
B cell-rich tertiary lymphoid structures (TLS) are associated with favorable prognosis and positive response to immunotherapy in cancer. Here we show that simultaneous activation of innate immune effectors, STING and lymphotoxin-β receptor (LTβR), results in CD8 + T cell-dependent tumor suppression while inducing high endothelial venule development and germinal center-like B cell responses in tumors to generate functional TLS in a T cell-dependent manner. In a neoadjuvant setting, activation of STING and LTβR by their agonists effectively immunized mice against tumor recurrence, leading to long-term survival. STING activation alone was insufficient for inducing B cell-containing TLS or eliciting long-term therapeutic effects. However, when combined with LTβR activation, it improved the fitness of TLS with B cell expansion and maturation to IgG-producing long-lived plasma cells and memory cells, increased CD4 + T cell recruitment and memory CD8 + T cell expansion, and shifted the T H 2/T H 17 balance, resulting in the potentiation of humoral and cellular immunity against tumors. These findings suggest a therapeutic approach of simultaneously activating STING and lymphotoxin pathways.
Related Topics
Concepts
Lymphotoxin
Germinal center
CD8
T cell
Immunology
Cancer research
Biology
Lymphotoxin beta receptor
B cell
Immune system
Antibody
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41590-025-02259-8
- https://www.nature.com/articles/s41590-025-02259-8.pdf
- OA Status
- hybrid
- Cited By
- 2
- References
- 62
- Related Works
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- OpenAlex ID
- https://openalex.org/W4413908379
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4413908379Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41590-025-02259-8Digital Object Identifier
- Title
-
Simultaneous STING and lymphotoxin-β receptor activation induces B cell responses in tertiary lymphoid structures to potentiate antitumor immunityWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-09-02Full publication date if available
- Authors
-
Junko Sawada, Yuzo Kikuchi, Maxwell Duah, José Luís Herrera, Fumiaki Kanamori, Krisztián Csomós, Tomoko Stansel, Nobuyoshi Hiraoka, Masayuki Yoshida, Jolán E. Walter, Carl F. Ware, Masanobu KomatsuList of authors in order
- Landing page
-
https://doi.org/10.1038/s41590-025-02259-8Publisher landing page
- PDF URL
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https://www.nature.com/articles/s41590-025-02259-8.pdfDirect link to full text PDF
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://www.nature.com/articles/s41590-025-02259-8.pdfDirect OA link when available
- Concepts
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Lymphotoxin, Germinal center, CD8, T cell, Immunology, Cancer research, Biology, Lymphotoxin beta receptor, B cell, Immune system, AntibodyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
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62Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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