Membrane IL-18 identifies a human macrophage subset with distinct proteomic and functional traits
This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display heterogeneous FOLR2 expression, distinguishing distinct cell subsets with possibly different functions. Accordingly, in primary neuroblastomas, transcriptional signatures associated with mIL-18 expression show different prognostic values. Our data show that mIL-18+ macrophages, which are predominant across the tumor microenvironment, exhibit previously undetected heterogeneity, potentially impacting tumor progression in a variable manner.
Authors
- Giuseppe Danilo Norata (ORCID: https://orcid.org/0000-0002-6081-1257)
- Fabrizio Loiacono (ORCID: https://orcid.org/0000-0001-9370-8910)
- Silvia Bruno (ORCID: https://orcid.org/0000-0002-7664-4545)
- Alessandra Dondero (ORCID: https://orcid.org/0000-0001-7340-8478)
- Santina Bruzzone (ORCID: https://orcid.org/0000-0003-2034-3716)
- Sonia Carta (ORCID: https://orcid.org/0000-0002-1278-9761)
- Massimo Locati (ORCID: https://orcid.org/0000-0003-3077-590X)
- Éric Vivier (ORCID: https://orcid.org/0000-0001-7022-8287)
- Martina Serra (ORCID: https://orcid.org/0000-0001-9200-9624)
- Martina Morini (ORCID: https://orcid.org/0000-0003-2569-4515)
- Cristina Bottino (ORCID: https://orcid.org/0000-0001-6695-1739)
- Francesca Bellora (ORCID: https://orcid.org/0000-0002-1932-0608)
- Pietro Arnaldi (ORCID: https://orcid.org/0000-0003-0274-8525)
- Marco Colonna (ORCID: https://orcid.org/0000-0001-5222-4987)
- Serafina Mammoliti (ORCID: https://orcid.org/0000-0002-6560-0061)
- Massimo Conte (ORCID: https://orcid.org/0000-0001-9405-7339)
- Chiara Vitale (ORCID: https://orcid.org/0000-0002-2865-1281)
- Roberta Castriconi (ORCID: https://orcid.org/0000-0003-2806-1115)
- Alberto Garaventa (ORCID: https://orcid.org/0000-0002-5368-6363)
- Chiara Lavarello (ORCID: https://orcid.org/0000-0002-5543-5285)
- Annamaria Pessino (ORCID: https://orcid.org/0000-0001-8040-378X)
- Davide Cangelosi (ORCID: https://orcid.org/0000-0002-6010-5619)
- Andrea Petretto (ORCID: https://orcid.org/0000-0001-7811-8517)
- Francesco Piacente (ORCID: https://orcid.org/0000-0001-5470-5987)
- Katia Cortese (ORCID: https://orcid.org/0000-0001-9218-8933)
Institutions
- Humanitas University (IT)
- University of Milan (IT)
- Washington University in St. Louis (US)
- Istituto Giannina Gaslini (IT)
- Assistance Publique Hôpitaux de Marseille (FR)
- Brain Injury Association of America (US)
- Château Gombert (FR)
- Hope Center for Neurological Disorders (US)
- Ospedale Bassini (IT)
- Innate Pharma (France) (FR)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Ospedale Policlinico San Martino (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Hôpital de la Timone (FR)
- University of Genoa (IT)
Publication Details
- Journal
- OncoImmunology
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1080/2162402x.2025.2571774
- Citations
- 1
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.80