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Articles by Pierre Bourdely
Distinct migratory dendritic cell subsets cooperate to prime tissue-resident memory-like CD8⁺ T cells in mouse tumors
Abstract Tumor-infiltrating tissue-resident memory (TRM)-like CD8+ T cells correlate with positive prognosis and better responses to cancer immunotherapy, yet the mechanisms underlying their specification remain ill-understood. Here, we use the KP (KrasG12D, p53-/-) mouse model of lung adenocarcinoma to investigate how different dendritic cell (DC) subsets shape tumor-specific CD8+ T cell responses.
Murine vascular organoids are responsive and adaptable 3D systems with cellular heterogeneity and dynamic plasticity
Abstract Blood vascular organoids (BVOs) have emerged as powerful tools for interrogating endothelial heterogeneity, function, and organ-specific cues during development, homeostasis, and disease. Here, we describe the stepwise generation and characterization of murine BVOs from different embryonic stem cells and introduce a fluorescent tracer system to follow their formation and maturation, visualizing functional and perfused vessels after transplantations into mice.
Intra-tumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1+ DC1 infiltration and activates anti-tumor immunity
Abstract Tumor infiltration by dendritic cells (DCs) has been identified as a biomarker associated with favorable outcomes and improved responses to immunotherapies by T cell immune checkpoint blockade. However, tumor induced immunosuppressive pathways contrive efficient DC infiltration. This calls for the development of DC-targeted interventions purposed to stimulate DC infiltration and local expansion.
The Rab32 small GTPase is required for efficient cross-priming of CD8+ T cells against cell-associated antigens by XCR1+ type 1 DCs in vivo.
Abstract Type 1 conventional dendritic cells (cDC1s) are critical for initiating adaptive immune responses through the cross-priming of CD8? T cells against antigens from tumor or virus-infected cells. This function depends on specialized cross-presentation pathways that allow cDC1s to process phagocytosed cell debris and present peptide–MHC I complexes. In this study, we identify the small GTPase Rab32 as being highly and selectively over-expressed in cDC1s as compared to cDC2s.
A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8+ T cell fitness in solid tumours - Nature Metabolism
Abstract Reprogramming T cell metabolism can improve intratumoural fitness. By performing a CRISPR/Cas9 metabolic survey in CD8+ T cells, we identified 83 targets and we applied single-cell RNA sequencing to disclose transcriptome changes associated with each metabolic perturbation in the context of pancreatic cancer. This revealed elongation of very long-chain fatty acids protein 1 (Elovl1) as a metabolic target to sustain effector functions and memory phenotypes in CD8+ T cells.
Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody‐Activated, Inducible Cross‐Presentation in Murine Type 2 DCs
1 Introduction Cross-presentation is the pathway by which exogenous antigens are processed and presented by professional antigen-presenting cells (pAPCs), via the class I Major Histocompatibility Complex (MHC-I), to T cells. This type of MHC-I antigen presentation is essential for the priming of cytotoxic T cells specific for viruses that do not infect pAPCs, intracellular bacteria, and tumors.[1, 2] The most efficient cross-presenting pAPCs are the dendritic cells (DCs).
DCs targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors
Abstract Cross-presentation by type 1 cDCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels of bona-fide neoantigens (neoAgs) remains unclear.
Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells
Highlights • DC3s are phenotypic and functional intermediates between cDC2s and monocytes • GM-CSF alone, but not FLT3L, supports efficient differentiation of DC3s • DC3s do not differentiate via cDC (CDP)- or monocyte-restricted (cMoP) progenitors • DC3s prime TRM cells in vitro and correlate with TRM expansion in primary breast cancer Summary Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation.
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