@article{EyrichRachorSchreiberetal.2013, author = {Eyrich, Matthias and Rachor, Johannes and Schreiber, Susanne C. and W{\"o}lfl, Matthias and Schlegel, Paul G.}, title = {Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives}, series = {Frontiers in Pediatrics}, journal = {Frontiers in Pediatrics}, doi = {10.3389/fped.2013.00012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96937}, year = {2013}, abstract = {Immunotherapy of malignant gliomas with autologous dendritic cells (DCs) in addition to surgery and radiochemotherapy has been a focus of intense research during the past decade. Since both children and adults are affected by this highly aggressive brain tumor, 10-15\% of the several hundred vaccinated patients represent children, making pediatric glioma patients the largest uniform pediatric vaccination cohort so far. In general, DC vaccination in malignant gliomas has been shown to be safe and several studies with a non-vaccinated control group could clearly demonstrate a survival benefit for the vaccinated patients. Interestingly, children and adolescents below 21 years of age seem to benefit even more than adult patients. This review summarizes the findings of the 25 clinical trials published so far and gives a perspective how DC vaccination could be implemented as part of multimodal therapeutic strategies in the near future.}, language = {en} } @article{GierlichLexTechnauetal.2020, author = {Gierlich, Philipp and Lex, Veronika and Technau, Antje and Keupp, Anne and Morper, Lorenz and Glunz, Amelie and Sennholz, Hanno and Rachor, Johannes and Sauer, Sascha and Marcu, Ana and Grigoleit, G{\"o}tz Ulrich and W{\"o}lfl, Matthias and Schlegel, Paul G. and Eyrich, Matthias}, title = {Prostaglandin E\(_2\) in a TLR3‑ and 7/8‑agonist‑based DC maturation cocktail generates mature, cytokine‑producing, migratory DCs but impairs antigen cross‑presentation to CD8\(^+\) T cells}, series = {Cancer Immunology, Immunotherapy}, volume = {69}, journal = {Cancer Immunology, Immunotherapy}, issn = {0340-7004}, doi = {10.1007/s00262-019-02470-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232311}, pages = {1029-1042}, year = {2020}, abstract = {Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E\(_2\) (PGE\(_2\)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8\(^+\) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8\(^+\) T-cells from na{\"i}ve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8\(^+\) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE2 during DC maturation and reproducible with several responder T-cell lines. In conclu-sion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE\(_2\) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides.}, language = {en} }