AUTHOR=Cornel Annelisa M. , van Til Niek P. , Boelens Jaap Jan , Nierkens Stefan TITLE=Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00982 DOI=10.3389/fimmu.2018.00982 ISSN=1664-3224 ABSTRACT=

Dendritic cell (DC) vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of surmountable shortcomings, such as selection of utilized DC subsets, DC loading and maturation strategies, as well as tumor-induced immunosuppression may be targeted to maximize anti-tumor responses of DC vaccines. Generation of DC from CD34+ hematopoietic stem and progenitor cells (HSPCs) may provide potential in patients undergoing allogeneic HSPC transplantations for hematologic malignancies. CD34+ HSPC from the graft can be genetically modified to optimize antigen presentation and to provide sufficient T cell stimulatory signals. We here describe beneficial (gene)-modifications that can be implemented in various processes in T cell activation by DC, among which major histocompatibility complex (MHC) class I and MHC class II presentation, DC maturation and migration, cross-presentation, co-stimulation, and immunosuppression to improve anti-tumor responses.