Projects per year
Abstract
CD8+ T cell killing of tumor cells is suppressed by the tumor microenvironment. Inhibitory receptors, prominently PD-1, are key mediators of this suppression. To discover cellular defects triggered by tumor exposure and associated PD-1 signaling, we have established an ex vivo imaging approach to investigate CD8+ tumor infiltrating lymphocytes (TILs) interacting with tumor targets. Whilst TIL:tumor cell couples still formed, couple stability deteriorated within 1-2 minutes. This was associated with impaired F-actin clearing from the center of the cellular interface, reduced calcium signaling, increased TIL locomotion and impaired tumor cell killing. Interaction of CD8+ lymphocytes with tumor cell spheroids in vitro induced a similar phenotype, supporting a critical role of direct T cell tumor cell contact. Diminished engagement of PD-1 within the tumor, but not acute ex vivo blockade, partially restored cell couple maintenance and killing. PD-1 thus suppresses TIL function by inducing a polarization-impaired state.
Original language | English |
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Article number | eaau4815 |
Journal | Science Signaling |
Volume | 13 |
Issue number | 649 |
DOIs | |
Publication status | Published - 15 Sept 2020 |
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Dive into the research topics of 'PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and tumor target cells within the tumor'. Together they form a unique fingerprint.Projects
- 1 Finished
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Causal modeling of T cell signaling in time and space - Proposal no. 7632552
Wuelfing, C. (Principal Investigator)
1/10/18 → 30/09/19
Project: Research
Profiles
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Professor Christoph Wuelfing
- School of Cellular and Molecular Medicine - Professor of Immunology
- Infection and Immunity
- Cancer
Person: Academic , Member