PMID- 38126310
OWN - NLM
STAT- MEDLINE
DCOM- 20240117
LR  - 20240121
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Print)
IS  - 1936-0851 (Linking)
VI  - 18
IP  - 2
DP  - 2024 Jan 16
TI  - Balancing the Nanoscale Organization in Multivalent Materials for Functional 
      Inhibition of the Programmed Death-1 Immune Checkpoint.
PG  - 1381-1395
LID - 10.1021/acsnano.3c06552 [doi]
AB  - Dendritic cells (DCs) regulate immune priming by expressing programmed death 
      ligand 1 (PD-L1) and PD-L2, which interact with the inhibitory receptor PD-1 on 
      activated T cells. PD-1 signaling regulates T cell effector functions and limits 
      autoimmunity. Tumor cells can hijack this pathway by overexpressing PD-L1 to 
      suppress antitumor T cell responses. Blocking this inhibitory pathway has been 
      beneficial for the treatment of various cancer types, although only a subset of 
      patients responds. A deepened understanding of the spatial organization and 
      molecular interplay between PD-1 and its ligands may inform the design of more 
      efficacious nanotherapeutics. We visualized the natural molecular PD-L1 
      organization on DCs by DNA-PAINT microscopy and created a template to engineer 
      DNA-based nanoclusters presenting PD-1 at defined valencies, distances, and 
      patterns. These multivalent nanomaterials were examined for their cellular 
      binding and blocking ability. Our data show that PD-1 nano-organization has 
      profound effects on ligand interaction and that the valency of PD-1 molecules 
      modulates the effectiveness in restoring T cell function. This work highlights 
      the power of spatially controlled functional materials to unravel the importance 
      of multivalent patterns in the PD-1 pathway and presents alternative design 
      strategies for immune-engineering.
FAU - Paloja, Kaltrina
AU  - Paloja K
AUID- ORCID: 0000-0001-8504-9919
AD  - Programmable Biomaterials Laboratory, Institute of Materials, School of 
      Engineering, Ecole Polytechnique Federale de Lausanne, Lausanne 1015, 
      Switzerland.
FAU - Weiden, Jorieke
AU  - Weiden J
AUID- ORCID: 0000-0002-2485-0590
AD  - Programmable Biomaterials Laboratory, Institute of Materials, School of 
      Engineering, Ecole Polytechnique Federale de Lausanne, Lausanne 1015, 
      Switzerland.
FAU - Hellmeier, Joschka
AU  - Hellmeier J
AUID- ORCID: 0000-0002-7153-9121
AD  - Max Planck Institute of Biochemistry, Planegg 82152, Germany.
FAU - Eklund, Alexandra S
AU  - Eklund AS
AUID- ORCID: 0000-0003-1047-2100
AD  - Max Planck Institute of Biochemistry, Planegg 82152, Germany.
FAU - Reinhardt, Susanne C M
AU  - Reinhardt SCM
AUID- ORCID: 0000-0003-0177-4801
AD  - Max Planck Institute of Biochemistry, Planegg 82152, Germany.
AD  - Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, 
      Munich 80539, Germany.
FAU - Parish, Ian A
AU  - Parish IA
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
AD  - Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 
      VIC 3128, Australia.
FAU - Jungmann, Ralf
AU  - Jungmann R
AUID- ORCID: 0000-0003-4607-3312
AD  - Max Planck Institute of Biochemistry, Planegg 82152, Germany.
AD  - Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, 
      Munich 80539, Germany.
FAU - Bastings, Maartje M C
AU  - Bastings MMC
AUID- ORCID: 0000-0002-7603-4018
AD  - Programmable Biomaterials Laboratory, Institute of Materials, School of 
      Engineering, Ecole Polytechnique Federale de Lausanne, Lausanne 1015, 
      Switzerland.
AD  - Interfaculty Bioengineering Institute, School of Engineering, Ecole Polytechnique 
      Federale de Lausanne, Lausanne 1015, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20231221
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Humans
MH  - *B7-H1 Antigen
MH  - Programmed Cell Death 1 Receptor
MH  - T-Lymphocytes
MH  - *Neoplasms/metabolism
MH  - DNA/metabolism
PMC - PMC10795474
OTO - NOTNLM
OT  - DNA origami
OT  - PD-1
OT  - T cell activation
OT  - dendritic cells
OT  - immune checkpoint blockade
OT  - multivalency
OT  - spatial organization
COIS- The authors declare no competing financial interest.
EDAT- 2023/12/21 12:42
MHDA- 2024/01/17 06:43
PMCR- 2024/01/18
CRDT- 2023/12/21 07:56
PHST- 2024/01/17 06:43 [medline]
PHST- 2023/12/21 12:42 [pubmed]
PHST- 2023/12/21 07:56 [entrez]
PHST- 2024/01/18 00:00 [pmc-release]
AID - 10.1021/acsnano.3c06552 [doi]
PST - ppublish
SO  - ACS Nano. 2024 Jan 16;18(2):1381-1395. doi: 10.1021/acsnano.3c06552. Epub 2023 
      Dec 21.