Human primed ILCPs support endothelial activation through NF-κB signaling

  1. Giulia Vanoni
  2. Giuseppe Ercolano
  3. Simona Candiani
  4. Mariangela Rutigliani
  5. Mariangela Lanata
  6. Laurent Derré
  7. Emanuela Marcenaro
  8. Pascal Schneider
  9. Pedro Romero
  10. Camilla Jandus  Is a corresponding author
  11. Sara Trabanelli  Is a corresponding author
  1. University of Lausanne - Ludwig Institute for Cancer Research, Switzerland
  2. University of Geneva, Switzerland
  3. University of Genova, Italy
  4. E.O. Galliera Hospital, Italy
  5. University Hospital of Lausanne (CHUV), Switzerland
  6. 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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3199-2412
  2. Giuseppe Ercolano

    Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Simona Candiani

    Department of Earth Science, Environment and Life, University of Genova, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Mariangela Rutigliani

    Department of Laboratory and Service, Histological and Anatomical Pathology, E.O. Galliera Hospital, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Mariangela Lanata

    Department of Laboratory and Service, Histological and Anatomical Pathology,, E.O. Galliera Hospital, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Laurent Derré

    Department of Urology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Emanuela Marcenaro

    Department of Experimental Medicine and Centre of Excellence for Biomedical Research, University of Genova, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Pascal Schneider

    Department of Biochemistry, University of Lausanne - Ludwig Institute for Cancer Research, Epalinges, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  9. Pedro Romero

    Department of Oncology, University of Lausanne, Epalinges, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  10. 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.
  11. 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.
    ORCID icon "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.

Reviewing Editor

  1. Vincenzo Cerullo, University of Helsinki, Finland

Version history

  1. Received: May 12, 2020
  2. Accepted: February 5, 2021
  3. Accepted Manuscript published: February 8, 2021 (version 1)
  4. Version of Record published: February 18, 2021 (version 2)

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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  1. Giulia Vanoni
  2. Giuseppe Ercolano
  3. Simona Candiani
  4. Mariangela Rutigliani
  5. Mariangela Lanata
  6. Laurent Derré
  7. Emanuela Marcenaro
  8. Pascal Schneider
  9. Pedro Romero
  10. Camilla Jandus
  11. Sara Trabanelli
(2021)
Human primed ILCPs support endothelial activation through NF-κB signaling
eLife 10:e58838.
https://doi.org/10.7554/eLife.58838

Share this article

https://doi.org/10.7554/eLife.58838

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