PD-L1 and ICOSL discriminate human Secretory and Helper dendritic cells in cancer, allergy and autoimmunity

Caroline Hoffmann (), Floriane Noel, Maximilien Grandclaudon, Lucile Massenet-Regad, Paula Michea, Philemon Sirven, Lilith Faucheux, Aurore Surun, Olivier Lantz, Mylene Bohec, Jian Ye, Weihua Guo, Juliette Rochefort, Jerzy Klijanienko, Sylvain Baulande, Charlotte Lecerf, Maud Kamal, Christophe Le Tourneau, Maude Guillot-Delost and Vassili Soumelis ()
Additional contact information
Caroline Hoffmann: Immunity and Cancer
Floriane Noel: Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis
Maximilien Grandclaudon: Immunity and Cancer
Lucile Massenet-Regad: Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis
Paula Michea: Institut Paoli Calmette, INSERM U1068—CNRS UMR7258—AMU UM105
Philemon Sirven: Immunity and Cancer
Lilith Faucheux: Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis
Aurore Surun: Institut Curie, SIREDO Cancer Center
Olivier Lantz: Immunity and Cancer
Mylene Bohec: Université Paris Sciences Lettres (PSL)
Jian Ye: City of Hope Comprehensive Cancer Center, Department of Immuno-Oncology
Weihua Guo: City of Hope Comprehensive Cancer Center, Department of Immuno-Oncology
Juliette Rochefort: Université de Paris
Jerzy Klijanienko: Université Paris Sciences Lettres (PSL)
Sylvain Baulande: Université Paris Sciences Lettres (PSL)
Charlotte Lecerf: Université Paris Sciences Lettres (PSL)
Maud Kamal: Université Paris Sciences Lettres (PSL)
Christophe Le Tourneau: Université Paris-Saclay
Maude Guillot-Delost: Immunity and Cancer
Vassili Soumelis: Immunity and Cancer

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract Dendritic cells (DC) are traditionally classified according to their ontogeny and their ability to induce T cell response to antigens, however, the phenotypic and functional state of these cells in cancer does not necessarily align to the conventional categories. Here we show, by using 16 different stimuli in vitro that activated DCs in human blood are phenotypically and functionally dichotomous, and pure cultures of type 2 conventional dendritic cells acquire these states (termed Secretory and Helper) upon appropriate stimuli. PD-L1highICOSLlow Secretory DCs produce large amounts of inflammatory cytokines and chemokines but induce very low levels of T helper (Th) cytokines following co-culturing with T cells. Conversely, PD-L1lowICOSLhigh Helper DCs produce low levels of secreted factors but induce high levels and a broad range of Th cytokines. Secretory DCs bear a single-cell transcriptomic signature indicative of mature migratory LAMP3+ DCs associated with cancer and inflammation. Secretory DCs are linked to good prognosis in head and neck squamous cell carcinoma, and to response to checkpoint blockade in Melanoma. Hence, the functional dichotomy of DCs we describe has both fundamental and translational implications in inflammation and immunotherapy.

Date: 2022
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DOI: 10.1038/s41467-022-29516-w

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