Human primed ILCPs support endothelial activation through NF-κB signaling
- University of Lausanne - Ludwig Institute for Cancer Research, Switzerland
- University of Geneva, Switzerland
- University of Genova, Italy
- E.O. Galliera Hospital, Italy
- University Hospital of Lausanne (CHUV), Switzerland
- University of Lausanne, Switzerland
Abstract
Innate lymphoid cells (ILCs) represent the most recently identified subset of effector lymphocytes, with key roles in the orchestration of early immune responses. Despite their established involvement in the pathogenesis of many inflammatory disorders, the role of ILCs in cancer remains poorly defined. Here we assessed whether human ILCs can actively interact with the endothelium to promote tumor growth control, favoring immune cell adhesion. We show that, among all ILC subsets, ILCPs elicited the strongest upregulation of adhesion molecules in ECs in vitro, mainly in a contact-dependent manner through the TNFR- and RANK-dependent engagement of the NF-κB pathway. Moreover, the ILCP-mediated activation of the ECs resulted to be functional by fostering the adhesion of other innate and adaptive immune cells. Interestingly, pre-exposure of ILCPs to human tumor cell lines strongly impaired this capacity. Hence, the ILCP-EC interaction might represent an attractive target to regulate the immune cell trafficking to tumor sites and, therefore, the establishment of an anti-tumor immune response.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PRIMA PR00P3_179727)
- Camilla Jandus
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (FNS 31003A_156469)
- Pedro Romero
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030A_176256)
- Pascal Schneider
Compagnia di San Paolo (2019.866)
- Emanuela Marcenaro
Compagnia di San Paolo (2019.866)
- Simona Candiani
Associazione Italiana per la Ricerca sul Cancro (AIRC 5x1000-21147)
- Emanuela Marcenaro
Associazione Italiana per la Ricerca sul Cancro (AIRC 5x1000-21147)
- Simona Candiani
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Vanoni et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Human primed ILCPs support endothelial activation through NF-κB signaling
eLife 10:e58838.
https://doi.org/10.7554/eLife.58838
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