20/06-2022 - Charles-Antoine DUTERTRE : The establishment of universal maps of human mononuclear phagocytes reveal tumour-specific macrophage and dendritic cell populations

15 - Juin - 2022

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 13h–14h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 20 JUIN 2022

The establishment of universal maps of human mononuclear phagocytes reveal tumour-specific macrophage and dendritic cell populations

Charles -Antoine DUTERTRE

Institut Gustave Roussy, Myeloid Cell Development Laboratory

invité par Equipe de François DELHOMMEAU, (Equipe DELHOMMEAU (francois.delhommeau@inserm.fr))

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Mononuclear phagocytes (MNP) encompass dendritic cells, monocytes and macrophages (MoMac), which exhibit antimicrobial, homeostatic and immunoregulatory functions. We integrated 178,651 MNP from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNP, and defined conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialised cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumour-associated macrophage populations. Particularly, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumour periphery in a T cell-dependent manner via IFN and CD40/CD40L-induced maturation from interferon-primed monocytes. IL4I1_Macs exhibited immune-suppressive characteristics through tryptophan degradation and promoted entry of regulatory T cell into tumours. From the MNP-VERSE, we also extracted and integrated 38,293 DC to to generate a DC single-cell RNA compendium (DC-VERSE). Using the DC-VERSE, we characterized DC subsets across tissues and found that all of the 11 neoplastic tissues included in the study contained Langerhans cell histiocytosis (LCH)-like CD207+ DC2 (that also specifically expressed CD1a) where their expansion: (1) inversely correlated with T cell clonality; (2) inversely correlated with tumour CD8+ resident memory T cells (TRM) in tumours; (3) positively correlated with terminally differentiated effector memory “exhausted” CD8+ T cells (TEMRA) in tumours; (3) was associated with lower patient survival.

This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

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