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

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). 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.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 incorporated in a database which constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (www.synmirapy.net/dc-optimization).

Regularity conditions and Farkas-type results for systems with fractional functions

This paper deals with some new versions of Farkas-type results for a system involving cone convex constraint, a geometrical constraint as well as a fractional function. We first introduce some new notions of regularity conditions in terms of the epigraphs of the conjugate functions. By using these regularity conditions, we obtain some new Farkas-type results for this system using an approach based on the theory of conjugate duality for convex or DC optimization problems. Moreover, we also show that some recently obtained results in the literature can be rediscovered as special cases of our main results.