Human primed ILCPs support endothelial activation through NF-κB signaling

Elife. 2021 Feb 8;10:e58838. doi: 10.7554/eLife.58838.

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 endothelial cells (ECs) in vitro, mainly in a contact-dependent manner through the tumor necrosis factor receptor- 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.

Keywords: NF-κB; cancer biology; endothelium; human; immunology; inflammation; innate lymphoid cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • Endothelial Cells / cytology
  • Endothelial Cells / immunology*
  • Endothelium / cytology
  • Endothelium / immunology
  • Humans
  • Immunity, Innate
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • NF-kappa B / genetics
  • NF-kappa B / immunology*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / immunology

Substances

  • Cell Adhesion Molecules
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.