Metallophilic marginal zone macrophages cross-prime CD8+ T cell-mediated protective immunity against blood-borne tumors
Mauvais FX, Hamel Y, Silvin A, Mulder K, Hildner K, Akyol R, Dalod M, Koumantou D, Saveanu L, Garfa M, Cagnard N, Bertocci B, Ginhoux F, van Endert P (2025)
Publication Language: English
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 58
Pages Range: 843-860.e20
Journal Issue: 4
DOI: 10.1016/j.immuni.2025.02.027
Abstract
Splenic metallophilic marginal zone macrophages (MMMs) are positioned to control the dissemination of blood-borne threats. We developed a purification protocol to enable characterization of MMMs phenotypically and transcriptionally. MMM gene expression profile was enriched for pathways associated with CD8+ T cell activation and major histocompatibility complex class I (MHC class I) cross-presentation. In vitro, purified MMMs equaled conventional dendritic cells type 1 (cDC1s) in cross-priming CD8+ T cells to soluble and particulate antigens, yet MMMs employed a distinct vacuolar processing pathway. In vivo biphoton and ex vivo light-sheet imaging showed long-standing contacts with cognate T cells differentiating to effectors. MMMs cross-primed protective CD8+ T cell antitumor responses both by capturing blood-borne tumor antigens and by internalizing tumor cells seeding the spleen. This cross-priming required expression of the transcription factor Batf3 by MMMs but was independent of cDC1-mediated capture of tumor material for cross-presentation or MHC class I-dressing. Thus, MMMs combine control of the dissemination of blood-borne pathogens and tumor materials with the initiation of innate and adaptive responses.
Authors with CRIS profile
Involved external institutions
Université Sorbonne Paris Cité
France (FR)
Institut Gustave-Roussy
France (FR)
Immunology Center of Marseille-Luminy
France (FR)
Université Paris Cité
France (FR)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
France (FR)
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
France (FR)
France (FR)
Institut Gustave-Roussy
France (FR)
Immunology Center of Marseille-Luminy
France (FR)
Université Paris Cité
France (FR)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
France (FR)
National Center for Scientific Research / Centre national de la recherche scientifique (CNRS)
France (FR)
How to cite
APA:
Mauvais, F.X., Hamel, Y., Silvin, A., Mulder, K., Hildner, K., Akyol, R.,... van Endert, P. (2025). Metallophilic marginal zone macrophages cross-prime CD8+ T cell-mediated protective immunity against blood-borne tumors. Immunity, 58(4), 843-860.e20. https://doi.org/10.1016/j.immuni.2025.02.027
MLA:
Mauvais, François Xavier, et al. "Metallophilic marginal zone macrophages cross-prime CD8+ T cell-mediated protective immunity against blood-borne tumors." Immunity 58.4 (2025): 843-860.e20.
BibTeX: Download