PMID- 33391542
OWN - NLM
STAT- MEDLINE
DCOM- 20210722
LR  - 20231110
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 11
IP  - 3
DP  - 2021
TI  - Network- and systems-based re-engineering of dendritic cells with non-coding RNAs 
      for cancer immunotherapy.
PG  - 1412-1428
LID - 10.7150/thno.53092 [doi]
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that induce and 
      regulate adaptive immunity by presenting antigens to T cells. Due to their 
      coordinative role in adaptive immune responses, DCs have been used as cell-based 
      therapeutic vaccination against cancer. The capacity of DCs to induce a 
      therapeutic immune response can be enhanced by re-wiring of cellular signalling 
      pathways with microRNAs (miRNAs). Methods: Since the activation and maturation of 
      DCs is controlled by an interconnected signalling network, we deploy an approach 
      that combines RNA sequencing data and systems biology methods to delineate 
      miRNA-based strategies that enhance DC-elicited immune responses. Results: 
      Through RNA sequencing of IKKbeta-matured DCs that are currently being tested in a 
      clinical trial on therapeutic anti-cancer vaccination, we identified 44 
      differentially expressed miRNAs. According to a network analysis, most of these 
      miRNAs regulate targets that are linked to immune pathways, such as cytokine and 
      interleukin signalling. We employed a network topology-oriented scoring model to 
      rank the miRNAs, analysed their impact on immunogenic potency of DCs, and 
      identified dozens of promising miRNA candidates, with miR-15a and miR-16 as the 
      top ones. The results of our analysis are presented in a database that 
      constitutes a tool to identify DC-relevant miRNA-gene interactions with 
      therapeutic potential (https://www.synmirapy.net/dc-optimization). Conclusions: 
      Our approach enables the systematic analysis and identification of functional 
      miRNA-gene interactions that can be experimentally tested for improving DC 
      immunogenic potency.
CI  - (c) The author(s).
FAU - Lai, Xin
AU  - Lai X
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Dreyer, Florian S
AU  - Dreyer FS
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Cantone, Martina
AU  - Cantone M
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Eberhardt, Martin
AU  - Eberhardt M
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Gerer, Kerstin F
AU  - Gerer KF
AD  - RNA Group, Department of Dermatology, Friedrich-Alexander-Universitat 
      Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Jaitly, Tanushree
AU  - Jaitly T
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Uebe, Steffen
AU  - Uebe S
AD  - Department of Human Genetics, Universitatsklinikum Erlangen, Erlangen, Germany.
FAU - Lischer, Christopher
AU  - Lischer C
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Ekici, Arif
AU  - Ekici A
AD  - Department of Human Genetics, Universitatsklinikum Erlangen, Erlangen, Germany.
FAU - Wittmann, Jurgen
AU  - Wittmann J
AD  - Division of Molecular Immunology, Department of Medicine 3, Universitatsklinikum 
      Erlangen, Erlangen, Germany.
FAU - Jack, Hans-Martin
AU  - Jack HM
AD  - Division of Molecular Immunology, Department of Medicine 3, Universitatsklinikum 
      Erlangen, Erlangen, Germany.
FAU - Schaft, Niels
AU  - Schaft N
AD  - RNA Group, Department of Dermatology, Friedrich-Alexander-Universitat 
      Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Dorrie, Jan
AU  - Dorrie J
AD  - RNA Group, Department of Dermatology, Friedrich-Alexander-Universitat 
      Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
FAU - Vera, Julio
AU  - Vera J
AD  - Laboratory of Systems Tumor Immunology, Department of Dermatology, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) and Universitatsklinikum 
      Erlangen, Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen, Erlangen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210101
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Untranslated)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Adaptive Immunity/immunology
MH  - Cancer Vaccines/immunology
MH  - Cells, Cultured
MH  - Cytokines/immunology
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - I-kappa B Kinase/immunology
MH  - Immunotherapy/methods
MH  - MicroRNAs/immunology
MH  - Neoplasms/*immunology/*therapy
MH  - RNA, Untranslated/*immunology
MH  - Signal Transduction/immunology
PMC - PMC7738891
OTO - NOTNLM
OT  - dendritic cell
OT  - microRNAs
OT  - network biology
OT  - systems biology
OT  - therapeutic vaccination in cancer
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2021/01/05 06:00
MHDA- 2021/07/23 06:00
PMCR- 2021/01/01
CRDT- 2021/01/04 05:28
PHST- 2020/09/10 00:00 [received]
PHST- 2020/10/15 00:00 [accepted]
PHST- 2021/01/04 05:28 [entrez]
PHST- 2021/01/05 06:00 [pubmed]
PHST- 2021/07/23 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - thnov11p1412 [pii]
AID - 10.7150/thno.53092 [doi]
PST - epublish
SO  - Theranostics. 2021 Jan 1;11(3):1412-1428. doi: 10.7150/thno.53092. eCollection 
      2021.