Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells
(1) Caro AA (2) Kancheva D (3) Hadadi E (4) Boeckx B (5) De Nolf C (6) Bardet PMR (7) Verstaen K (8) Li L (9) Oueslati L (10) Figueras-Duch N (11) Elkrim Y (12) Vandamme N (13) Deschoemaeker S (14) Blomme A (15) Close P (16) Janssens S (17) De Palma M (18) Lambrechts D (19) Coosemans A (20) Laoui D
Caro and Kancheva et al. generated comprehensive scRNAseq atlases of tumor-associated mononuclear phagocytes (monocytes, macrophages, DCs, and pDCs) across 14 mouse and 10 human cancer settings. 31 murine and 25 human lineage-defined tumor-associated DC (TADC) subsets were identified across cDC1, cDC2A, cDC2B, and DC3 subsets. In tumors, new clusters emerged early on, and as tumors progressed, TADCs adopted a more inflammatory, but eventually less mature phenotype Tumor-mediated reprogramming was also evident within lymph node DCs. In patient data, certain TADC subsets and states were associated with patient outcomes.
Contributed by Lauren Hitchings
(1) Caro AA (2) Kancheva D (3) Hadadi E (4) Boeckx B (5) De Nolf C (6) Bardet PMR (7) Verstaen K (8) Li L (9) Oueslati L (10) Figueras-Duch N (11) Elkrim Y (12) Vandamme N (13) Deschoemaeker S (14) Blomme A (15) Close P (16) Janssens S (17) De Palma M (18) Lambrechts D (19) Coosemans A (20) Laoui D
Caro and Kancheva et al. generated comprehensive scRNAseq atlases of tumor-associated mononuclear phagocytes (monocytes, macrophages, DCs, and pDCs) across 14 mouse and 10 human cancer settings. 31 murine and 25 human lineage-defined tumor-associated DC (TADC) subsets were identified across cDC1, cDC2A, cDC2B, and DC3 subsets. In tumors, new clusters emerged early on, and as tumors progressed, TADCs adopted a more inflammatory, but eventually less mature phenotype Tumor-mediated reprogramming was also evident within lymph node DCs. In patient data, certain TADC subsets and states were associated with patient outcomes.
Contributed by Lauren Hitchings
ABSTRACT: Dendritic cells (DCs) are critical inducers of anti-tumor immunity. To achieve a comprehensive mapping of mouse and human DC subsets and states in a cancer context, here we generate pan-cancer mouse and human tumor-associated DC (TADC) scRNA-seq atlases, encompassing 14 mouse tumor models and 10 human cancer types, within which we identify several lineage-defined DC subsets along with maturation/functional states. We show that TADCs acquire an inflammatory profile with tumor progression and that tumor-mediated reprogramming occurs within the DCs from lymph nodes of tumor-bearing mice. Importantly, we demonstrate that TADCs are broadly conserved between mice and humans, although species-specific differences may exist in some subsets and states. Moreover, we present a comprehensive assessment of how different human TADC clusters associate with patient survival outcomes. Overall, we provide an in-depth characterization of the TADC compartment in mouse and human cancers, which can improve our understanding of the tumor microenvironment and contribute to the development of new anti-cancer therapies.
Author Info:
(1) Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. Lab of Cellular and Molecular Immunology, Brussels Center for I
mmunology, Vrije Universiteit Brussel, Brussels, Belgium. Lab of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. (2) Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. (3) Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. (4) Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium. Laboratory for Translational Genetics, VIB Center for Cancer Biology, Leuven, Belgium. (5) Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium. Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium. Laboratory for Barriers in Inflammation, VIB Center for Inflammation Research, Ghent, Belgium. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. (6) Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. (7) Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. VIB Single Cell Core; VIB, Ghent-Leuven, Belgium. (8) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland. Agora Cancer Research Center, Lausanne, Switzerland. (9) Laboratory of Cancer Signaling, GIGA-Institute, University of Lige, Lige, Belgium. (10) Laboratory of Cancer Signaling, GIGA-Institute, University of Lige, Lige, Belgium. (11) Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. (12) Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. VIB Single Cell Core; VIB, Ghent-Leuven, Belgium. (13) Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. (14) Laboratory of Cancer Signaling, GIGA-Institute, University of Lige, Lige, Belgium. Laboratory of Metabolic Regulation, GIGA-Institute, University of Lige, Lige, Belgium. (15) Laboratory of Cancer Signaling, GIGA-Institute, University of Lige, Lige, Belgium. WELBIO Department, WEL Research Institute, Wavre, Belgium. (16) Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium. Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium. (17) Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland. Agora Cancer Research Center, Lausanne, Switzerland. (18) Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium. Laboratory for Translational Genetics, VIB Center for Cancer Biology, Leuven, Belgium. (19) Lab of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. (20) Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. dlaoui@vub.be. Lab of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium. dlaoui@vub.be.
