T cell‐dependent bispecific antibodies alter organ‐specific endothelial cell–T cell interaction
Abstract: Preclinical and clinical studies demonstrate that T cell‐dependent bispecific antibodies (TDBs) induce systemic changes in addition to tumor killing, leading to adverse events. Here, we report an in‐depth characterization of acute responses to TDBs in tumor‐bearing mice. Contrary to modest changes in tumors, rapid and substantial lymphocyte accumulation and endothelial cell (EC) activation occur around large blood vessels in normal organs including the liver. We hypothesize that organ‐specific ECs may account for the differential responses in normal tissues and tumors, and we identify a list of genes selectively upregulated by TDB in large liver vessels. Using one of the genes as an example, we demonstrate that CD9 facilitates ICAM‐1 to support T cell–EC interaction in response to soluble factors released from a TDB‐mediated cytotoxic reaction. Our results suggest that multiple factors may cooperatively promote T cell infiltration into normal organs as a secondary response to TDB‐mediated tumor killing. These data shed light on how different vascular beds respond to cancer immunotherapy and may help improve their safety and efficacy.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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T cell‐dependent bispecific antibodies alter organ‐specific endothelial cell–T cell interaction ; day:09 ; month:01 ; year:2023 ; extent:23
EMBO reports / European Molecular Biology Organization ; (09.01.2023) (gesamt 23)
- Urheber
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Himmels, Patricia
Nguyen, Thi Thu Thao
Mitzner, Maresa Caunt
Arrazate, Alfonso
Yeung, Stacey
Burton, Jeremy
Clark, Robyn
Totpal, Klara
Jesudason, Raj
Yang, Angela
Solon, Margaret
Eastham, Jeffrey
Modrusan, Zora
Webster, Joshua D.
Lo, Amy A.
Piskol, Robert
Ye, Weilan
- DOI
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10.15252/embr.202255532
- URN
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urn:nbn:de:101:1-2023010914133328460095
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
- 15.08.2025, 07:22 MESZ
Datenpartner
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Beteiligte
- Himmels, Patricia
- Nguyen, Thi Thu Thao
- Mitzner, Maresa Caunt
- Arrazate, Alfonso
- Yeung, Stacey
- Burton, Jeremy
- Clark, Robyn
- Totpal, Klara
- Jesudason, Raj
- Yang, Angela
- Solon, Margaret
- Eastham, Jeffrey
- Modrusan, Zora
- Webster, Joshua D.
- Lo, Amy A.
- Piskol, Robert
- Ye, Weilan
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