PMID- 31244860
OWN - NLM
STAT- MEDLINE
DCOM- 20200716
LR  - 20200716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on 
      Different Subsets of Dendritic Cells.
PG  - 1325
LID - 10.3389/fimmu.2019.01325 [doi]
LID - 1325
AB  - Dendritic cells (DCs) play a crucial role in initiating and shaping immune 
      responses. The effects of DCs on adaptive immune responses depend partly on 
      functional specialization of distinct DC subsets, and partly on the activation 
      state of DCs, which is largely dictated by environmental signals. Fully activated 
      immunostimulatory DCs express high levels of costimulatory molecules, produce 
      pro-inflammatory cytokines, and stimulate T cell proliferation, whereas 
      tolerogenic DCs express low levels of costimulatory molecules, produce 
      immunomodulatory cytokines and impair T cell proliferation. Relevant to the 
      increasing use of immune checkpoint blockade in cancer treatment, signals 
      generated from inhibitory checkpoint molecules on DC surface may also contribute 
      to the inhibitory properties of tolerogenic DCs. Yet, our knowledge on the 
      expression of inhibitory molecules on human DC subsets is fragmentary. Therefore, 
      in this study, we investigated the expression of three immune checkpoints on 
      peripheral blood DC subsets, in basal conditions and upon exposure to 
      pro-inflammatory and anti-inflammatory stimuli, by using a flow cytometric panel 
      that allows a direct comparison of the activatory/inhibitory phenotype of 
      DC-lineage and inflammatory DC subsets. We demonstrated that functionally 
      distinct DC subsets are characterized by differential expression of activatory 
      and inhibitory molecules, and that cDC1s in particular are endowed with a unique 
      immune checkpoint repertoire characterized by high TIM-3 expression, scarce PD-L1 
      expression and lack of ILT2. Notably, this unique cDC1 repertoire was subverted 
      in a group of patients with myelodysplastic syndromes included in the study. 
      Applied to the characterization of DCs in the tumor microenvironment, this panel 
      has the potential to provide valuable information to be used for investigating 
      the role of DC subsets in cancer, guiding DC-targeting treatments, and possibly 
      identifying predictive biomarkers for clinical response to cancer immunotherapy.
FAU - Carenza, Claudia
AU  - Carenza C
AD  - Department of Medical Biotechnologies and Translational Medicine, University of 
      Milan, Milan, Italy.
AD  - Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research 
      Center, Rozzano, Italy.
FAU - Calcaterra, Francesca
AU  - Calcaterra F
AD  - Department of Medical Biotechnologies and Translational Medicine, University of 
      Milan, Milan, Italy.
AD  - Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research 
      Center, Rozzano, Italy.
FAU - Oriolo, Ferdinando
AU  - Oriolo F
AD  - Department of Medical Biotechnologies and Translational Medicine, University of 
      Milan, Milan, Italy.
AD  - Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research 
      Center, Rozzano, Italy.
FAU - Di Vito, Clara
AU  - Di Vito C
AD  - Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research 
      Center, Rozzano, Italy.
FAU - Ubezio, Marta
AU  - Ubezio M
AD  - Cancer Center, Humanitas Reserach Hospital, Rozzano, Italy.
FAU - Della Porta, Matteo Giovanni
AU  - Della Porta MG
AD  - Cancer Center, Humanitas Reserach Hospital, Rozzano, Italy.
AD  - Humanitas University, Rozzano, Italy.
FAU - Mavilio, Domenico
AU  - Mavilio D
AD  - Department of Medical Biotechnologies and Translational Medicine, University of 
      Milan, Milan, Italy.
AD  - Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research 
      Center, Rozzano, Italy.
FAU - Della Bella, Silvia
AU  - Della Bella S
AD  - Department of Medical Biotechnologies and Translational Medicine, University of 
      Milan, Milan, Italy.
AD  - Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research 
      Center, Rozzano, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190611
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens, CD)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Cytokines)
RN  - 0 (HAVCR2 protein, human)
RN  - 0 (Hepatitis A Virus Cellular Receptor 2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (LILRB1 protein, human)
RN  - 0 (Leukocyte Immunoglobulin-like Receptor B1)
SB  - IM
MH  - Adaptive Immunity
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, CD/metabolism
MH  - B7-H1 Antigen/metabolism
MH  - Cell Lineage/immunology
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/classification/*immunology/metabolism
MH  - Female
MH  - Flow Cytometry/methods
MH  - Healthy Volunteers
MH  - Hepatitis A Virus Cellular Receptor 2/metabolism
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Leukocyte Immunoglobulin-like Receptor B1/metabolism
MH  - Male
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/blood/immunology
MH  - Young Adult
PMC - PMC6579930
OTO - NOTNLM
OT  - ILT2
OT  - PD-L1
OT  - TIM-3
OT  - conventional cDC1 dendritic cells
OT  - conventional cDC2 dendritic cells
OT  - immune checkpoint
OT  - myelodysplastic syndromes
OT  - plasmacytoid dendritic cells
EDAT- 2019/06/28 06:00
MHDA- 2020/07/17 06:00
PMCR- 2019/01/01
CRDT- 2019/06/28 06:00
PHST- 2019/01/23 00:00 [received]
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/06/28 06:00 [entrez]
PHST- 2019/06/28 06:00 [pubmed]
PHST- 2020/07/17 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01325 [doi]
PST - epublish
SO  - Front Immunol. 2019 Jun 11;10:1325. doi: 10.3389/fimmu.2019.01325. eCollection 
      2019.