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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
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
- Vincenzo Cerullo, University of Helsinki, Finland
Version history
- Received: May 12, 2020
- Accepted: February 5, 2021
- Accepted Manuscript published: February 8, 2021 (version 1)
- 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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Human primed ILCPs support endothelial activation through NF-κB signaling
eLife 10:e58838.
https://doi.org/10.7554/eLife.58838
Further reading
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Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development.
