Impaired circulating myeloid CD1c+ dendritic cell function in human glioblastoma is restored by p38 inhibition - implications for the next generation of DC vaccines

Adhikaree, Jason; Franks, Hester Ann; Televantos, Constantinos; Vaghela, Poonam; Kaur, Aanchal Preet; Walker, David; Schmitz, Marc; Jackson, Andrew; Patel, Poulam Manubhai

Abstract

Current treatments for glioblastoma (GBM) have limited efficacy and significant morbidity and therefore new strategies are urgently needed. Dendritic cells have the power to create anti-tumour immune responses. The greater potency of circulating dendritic cells (DC) over laboratory-generated monocyte-derived DC makes them exciting new immunotherapeutic candidates. To determine the immune status of GBM patients we initially investigated the frequency and function of circulating DC subsets. Furthermore, we tested the therapeutic potential of inhibiting the p38 mitogen-activated protein kinase pathway (p38i) in circulating DC to overcome DC dysfunction.
GBM patients (n=16) had significantly reduced numbers of the major myeloid circulating dendritic cell (cDC2) and plasmacytoid DC vs healthy controls; 1736 vs 4975 (p=0.028) and 893 vs 2287 cells/mL (P=

Citation

Adhikaree, J., Franks, H. A., Televantos, C., Vaghela, P., Kaur, A. P., Walker, D., Schmitz, M., Jackson, A., & Patel, P. M. (2019). Impaired circulating myeloid CD1c+ dendritic cell function in human glioblastoma is restored by p38 inhibition - implications for the next generation of DC vaccines. OncoImmunology, 8(7), 1-12. https://doi.org/10.1080/2162402X.2019.1593803

• Journal Article Type: Article
• Acceptance Date: Feb 28, 2019
• Online Publication Date: Apr 13, 2019
• Publication Date: Apr 13, 2019
• Deposit Date: Mar 1, 2019
• Publicly Available Date: Jun 11, 2019
• Journal: OncoImmunology
• Print ISSN: 2162-4011
• Electronic ISSN: 2162-402X
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 7
• Article Number: 1593803
• Pages: 1-12
• DOI: https://doi.org/10.1080/2162402X.2019.1593803
• Keywords: Immunology; Immunology and Allergy; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/1594839
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/2162402X.2019.1593803
• Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Oncoimmunology on 13.04.2019, available online: http://www.tandfonline.com/10.1080/2162402X.2019.1593803
• Contract Date: Mar 1, 2019