Human primed ILCPs support endothelial activation through NF-κB signaling

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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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Giulia Vanoni

Department of Oncology, University of Lausanne - Ludwig Institute for Cancer Research, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3199-2412
Giuseppe Ercolano

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland

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The authors declare that no competing interests exist.
Simona Candiani

Department of Earth Science, Environment and Life, University of Genova, Genova, Italy

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The authors declare that no competing interests exist.
Mariangela Rutigliani

Department of Laboratory and Service, Histological and Anatomical Pathology, E.O. Galliera Hospital, Genova, Italy

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The authors declare that no competing interests exist.
Mariangela Lanata

Department of Laboratory and Service, Histological and Anatomical Pathology,, E.O. Galliera Hospital, Genova, Italy

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The authors declare that no competing interests exist.
Laurent Derré

Department of Urology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland

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The authors declare that no competing interests exist.
Emanuela Marcenaro

Department of Experimental Medicine and Centre of Excellence for Biomedical Research, University of Genova, Genova, Italy

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The authors declare that no competing interests exist.
Pascal Schneider

Department of Biochemistry, University of Lausanne - Ludwig Institute for Cancer Research, Epalinges, Switzerland

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The authors declare that no competing interests exist.
Pedro Romero

Department of Oncology, University of Lausanne, Epalinges, Switzerland

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The authors declare that no competing interests exist.
Camilla Jandus

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland

For correspondence
camilla.jandus@unige.ch

Competing interests
The authors declare that no competing interests exist.
Sara Trabanelli

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland

For correspondence
sara.trabanelli@unige.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8648-1324

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

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.