Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy

Lai X, Dreyer F, Cantone M, Eberhardt M, Gerer KF, Jaitly T, Uebe S, Lischer C, Ekici AB, Wittmann J, Jäck HM, Schaft N, Dörrie J, Vera J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Theranostics Ivyspring International Publisher

Book Volume: 11

Pages Range: 1412-1428

Journal Issue: 3

URI: https://www.researchgate.net/publication/345993774_Network-_and_systems-based_re-engineering_of_dendritic_cells_with_non-coding_RNAs_for_cancer_immunotherapy

DOI: 10.7150/thno.53092

Abstract

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 IKKβ-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 (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.

Authors with CRIS profile

Xin Lai Department of Dermatology Florian Dreyer Department of Dermatology Martina Cantone Department of Dermatology Martin Eberhardt Department of Dermatology Steffen Uebe Institute of Human Genetics Christopher Lischer Department of Dermatology Arif Bülent Ekici Institute of Human Genetics Jürgen Wittmann Department of Molecular Immunology Hans-Martin Jäck Department of Molecular Immunology Niels Schaft Department of Dermatology Jan Dörrie Department of Dermatology Julio Vera González Professur für Tumorimmunologie (Schwerpunkt Systembiologie)

How to cite

APA:

Lai, X., Dreyer, F., Cantone, M., Eberhardt, M., Gerer, K.F., Jaitly, T.,... Vera, J. (2021). Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy. Theranostics, 11(3), 1412-1428. https://doi.org/10.7150/thno.53092

MLA:

Lai, Xin, et al. "Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy." Theranostics 11.3 (2021): 1412-1428.

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