The roles of different forms of IL-15 in human melanoma progression.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 10 03 2023
accepted: 05 05 2023
medline: 20 6 2023
pubmed: 19 6 2023
entrez: 19 6 2023
Statut: epublish

Résumé

Melanoma is a lethal skin cancer, and the risk of developing it is increased by exposure to ultraviolet (UV) radiation. The production of cytokines such as interleukin-15 (IL-15), induced by the exposure of skin cells to UV rays, could also promote melanoma development. The aim of this study is to investigate the possible role of Interleukin-15/Interleukin-15 Receptor α (IL-15/IL-15Rα) complexes in melanoma development. The expression of IL-15/IL-15Rα complexes by melanoma cells was evaluated both Analysis of a melanoma tissue microarray shows a significant increase in the number of IL-15 Membrane-bound and secreted IL-15/IL-15Rα complexes are continuously present during progression in melanoma. It is notable that, although IL-15/IL-15Rα initially promoted the production of cytotoxic T and NK cells, at stage IV promotion of the development of anergic and dysfunctional cytotoxic NK cells was observed. In a subgroup of melanoma metastatic patients, the continuous secretion of high amounts of the soluble complex could represent a novel NK cell immune escape mechanism.

Sections du résumé

Background
Melanoma is a lethal skin cancer, and the risk of developing it is increased by exposure to ultraviolet (UV) radiation. The production of cytokines such as interleukin-15 (IL-15), induced by the exposure of skin cells to UV rays, could also promote melanoma development. The aim of this study is to investigate the possible role of Interleukin-15/Interleukin-15 Receptor α (IL-15/IL-15Rα) complexes in melanoma development.
Methods
The expression of IL-15/IL-15Rα complexes by melanoma cells was evaluated both
Results
Analysis of a melanoma tissue microarray shows a significant increase in the number of IL-15
Conclusions
Membrane-bound and secreted IL-15/IL-15Rα complexes are continuously present during progression in melanoma. It is notable that, although IL-15/IL-15Rα initially promoted the production of cytotoxic T and NK cells, at stage IV promotion of the development of anergic and dysfunctional cytotoxic NK cells was observed. In a subgroup of melanoma metastatic patients, the continuous secretion of high amounts of the soluble complex could represent a novel NK cell immune escape mechanism.

Identifiants

pubmed: 37334356
doi: 10.3389/fimmu.2023.1183668
pmc: PMC10272795
doi:

Substances chimiques

Antineoplastic Agents 0
Interleukin-15 0
Interleukin-15 Receptor alpha Subunit 0
IL15 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1183668

Informations de copyright

Copyright © 2023 Di Matteo, Munari, Fiore, Santopolo, Sampaoli, Pelosi, Chouaib, Tumino, Vacca, Mariotti, Ebert, Machwirth, Haas, Pezzullo, Pietra, Grottoli, Buart, Mortier, Maggi, Moretta, Caruana and Azzarone.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Sabina Di Matteo (S)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Enrico Munari (E)

Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Piera Filomena Fiore (PF)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Silvia Santopolo (S)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Camilla Sampaoli (C)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Andrea Pelosi (A)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Salem Chouaib (S)

Institut national de la santé et de la recherche médicale Unitè Mixte Rechercce (INSERM UMR) 1186, Integrative Tumor Immunology and Cancer Immunotherapy, Gustave Roussy, École Pratique des Hautes Études (EPHE), Faculty De Médecine Univ. Paris-Sud, University Paris-Saclay, Villejuif, France.
Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab Emirates.

Nicola Tumino (N)

Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Paola Vacca (P)

Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Francesca Romana Mariotti (FR)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Stefan Ebert (S)

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Würzburg, Würzburg, Germany.

Markus Machwirth (M)

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Würzburg, Würzburg, Germany.

Dorothee Haas (D)

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Würzburg, Würzburg, Germany.

Marco Pezzullo (M)

Core Facility, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.

Gabriella Pietra (G)

Department of Experimental Medicine (DiMES), University of Genoa, Genoa, Italy.
Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Melania Grottoli (M)

Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Stephanie Buart (S)

Institut national de la santé et de la recherche médicale Unitè Mixte Rechercce (INSERM UMR) 1186, Integrative Tumor Immunology and Cancer Immunotherapy, Gustave Roussy, École Pratique des Hautes Études (EPHE), Faculty De Médecine Univ. Paris-Sud, University Paris-Saclay, Villejuif, France.

Erwan Mortier (E)

Nantes Université, Centre national de la recherche scientifique (CNRS), Inserm, CRCI2NA, Nantes, France.
LabEx IGO, Immunotherapy, Graft, Oncology, Nantes, France.

Enrico Maggi (E)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Lorenzo Moretta (L)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Ignazio Caruana (I)

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Würzburg, Würzburg, Germany.

Bruno Azzarone (B)

Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

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Classifications MeSH