PMID- 37996514
OWN - NLM
STAT- MEDLINE
DCOM- 20240229
LR  - 20240301
IS  - 2662-1347 (Electronic)
IS  - 2662-1347 (Linking)
VI  - 5
IP  - 2
DP  - 2024 Feb
TI  - Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer 
      immunotherapy.
PG  - 240-261
LID - 10.1038/s43018-023-00668-y [doi]
AB  - Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell 
      activation, trafficking and function. Monocyte-derived DCs pulsed with tumor 
      antigens have been tested extensively for therapeutic vaccination in cancer, with 
      mixed clinical results. Here, we present a cell-therapy platform based on mouse 
      or human DC progenitors (DCPs) engineered to produce two immunostimulatory 
      cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional 
      type-I DCs (cDC1) and suppressed tumor growth, including melanoma and 
      autochthonous liver models, without the need for antigen loading or myeloablative 
      host conditioning. Tumor response involved synergy between IL-12 and FLT3L and 
      was associated with natural killer and T cell infiltration and activation, 
      M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity 
      was dependent on endogenous cDC1 expansion and interferon-gamma signaling but did not 
      require CD8(+) T cell cytotoxicity. Cytokine-armed DCPs synergized effectively 
      with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial 
      gliomas in mice, illustrating their potential in combination therapies.
CI  - (c) 2023. The Author(s).
FAU - Ghasemi, Ali
AU  - Ghasemi A
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Martinez-Usatorre, Amaia
AU  - Martinez-Usatorre A
AUID- ORCID: 0000-0002-3416-1529
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Li, Luqing
AU  - Li L
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Hicham, Mehdi
AU  - Hicham M
AUID- ORCID: 0000-0002-9979-4757
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Guichard, Alan
AU  - Guichard A
AUID- ORCID: 0000-0001-8623-9570
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Marcone, Rachel
AU  - Marcone R
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Translational Data Science (TDS) Facility, Swiss Institute of Bioinformatics 
      (SIB), Lausanne, Switzerland.
FAU - Fournier, Nadine
AU  - Fournier N
AUID- ORCID: 0000-0002-9347-7929
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Translational Data Science (TDS) Facility, Swiss Institute of Bioinformatics 
      (SIB), Lausanne, Switzerland.
FAU - Torchia, Bruno
AU  - Torchia B
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Martinez Bedoya, Darel
AU  - Martinez Bedoya D
AUID- ORCID: 0000-0002-1603-5801
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
AD  - Center for Translational Research in Onco-Hematology, University of Geneva 
      (UNIGE), Geneva, Switzerland.
FAU - Davanture, Suzel
AU  - Davanture S
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
AD  - Center for Translational Research in Onco-Hematology, University of Geneva 
      (UNIGE), Geneva, Switzerland.
FAU - Fernandez-Vaquero, Mirian
AU  - Fernandez-Vaquero M
AD  - Division of Chronic Inflammation and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
FAU - Fan, Chaofan
AU  - Fan C
AD  - Division of Chronic Inflammation and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
FAU - Janzen, Jakob
AU  - Janzen J
AD  - Division of Chronic Inflammation and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
FAU - Mohammadzadeh, Yahya
AU  - Mohammadzadeh Y
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Genolet, Raphael
AU  - Genolet R
AD  - Ludwig Institute for Cancer Research, Lausanne, Switzerland.
AD  - Department of Oncology, University of Lausanne (UNIL) and Lausanne University 
      Hospital (CHUV), Lausanne, Switzerland.
FAU - Mansouri, Nahal
AU  - Mansouri N
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
FAU - Wenes, Mathias
AU  - Wenes M
AUID- ORCID: 0000-0001-8478-8592
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
AD  - Center for Translational Research in Onco-Hematology, University of Geneva 
      (UNIGE), Geneva, Switzerland.
FAU - Migliorini, Denis
AU  - Migliorini D
AUID- ORCID: 0000-0003-0151-3222
AD  - Agora Cancer Research Center, Lausanne, Switzerland.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland.
AD  - Center for Translational Research in Onco-Hematology, University of Geneva 
      (UNIGE), Geneva, Switzerland.
AD  - Department of Oncology, Geneva University Hospital (HUG), Geneva, Switzerland.
FAU - Heikenwalder, Mathias
AU  - Heikenwalder M
AUID- ORCID: 0000-0002-3135-2274
AD  - Division of Chronic Inflammation and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
AD  - The M3 Research Center, Eberhard Karls University, Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC 2180), Eberhard Karls University, Tubingen, 
      Germany.
FAU - De Palma, Michele
AU  - De Palma M
AUID- ORCID: 0000-0001-9128-5459
AD  - Swiss Institute for Experimental Cancer Research (ISREC), School of Life 
      Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, 
      Switzerland. michele.depalma@epfl.ch.
AD  - Agora Cancer Research Center, Lausanne, Switzerland. michele.depalma@epfl.ch.
AD  - Swiss Cancer Center Leman (SCCL), Lausanne, Switzerland. michele.depalma@epfl.ch.
LA  - eng
GR  - EVOLVE-725051/EC | EU Framework Programme for Research and Innovation H2020 | 
      H2020 Priority Excellent Science | H2020 European Research Council (H2020 
      Excellent Science - European Research Council)/
PT  - Journal Article
DEP - 20231123
PL  - England
TA  - Nat Cancer
JT  - Nature cancer
JID - 101761119
RN  - 0 (Cytokines)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Cytokines
MH  - Immunotherapy
MH  - Dendritic Cells
MH  - *Neoplasms/therapy
MH  - Interleukin-12
PMC - PMC10899110
COIS- M.D.P. has received sponsored research grants from EVIR Therapeutics, Hoffmann 
      La-Roche and Deciphera Pharmaceuticals, serves on the Scientific Advisory Boards 
      of EVIR Therapeutics, Montis Biosciences, Macomics, Deciphera Pharmaceuticals, 
      Light Chain Bioscience/Novimmune and Genenta, and is an inventor on patents on 
      engineered DCs filed by EPFL. D.M. is a consultant for Limula and MPC 
      Therapeutics, scientific co-founder of Cellula Therapeutics and is an inventor on 
      patents related to CAR-T cell therapy filed by the University of Pennsylvania, 
      Istituto Oncologico della Svizzera Italiana (IOSI) and the University of Geneva. 
      The other authors declare no conflict of interest.
EDAT- 2023/11/24 00:42
MHDA- 2024/02/29 06:42
PMCR- 2023/11/23
CRDT- 2023/11/23 23:30
PHST- 2023/03/17 00:00 [received]
PHST- 2023/10/11 00:00 [accepted]
PHST- 2024/02/29 06:42 [medline]
PHST- 2023/11/24 00:42 [pubmed]
PHST- 2023/11/23 23:30 [entrez]
PHST- 2023/11/23 00:00 [pmc-release]
AID - 10.1038/s43018-023-00668-y [pii]
AID - 668 [pii]
AID - 10.1038/s43018-023-00668-y [doi]
PST - ppublish
SO  - Nat Cancer. 2024 Feb;5(2):240-261. doi: 10.1038/s43018-023-00668-y. Epub 2023 Nov 
      23.