Hoyer S, Eberlein V, Schuler G, Berking C, Heinzerling L, Schaft N, Dörrie J (2021)
Publication Type: Journal article, Original article
Publication year: 2021
Original Authors: Stefanie Hoyer, Valentina Eberlein, Gerold Schuler, Carola Berking, Lucie Heinzerling, Niels Schaft, Jan Dörrie
Book Volume: 22
Pages Range: 11951
Issue: 21
BRAF and MEK inhibitor (BRAFi/MEKi) combinations are currently the standard treatment for patients with BRAFV600 mutant metastatic melanoma. Since the RAS/RAF/MEK/ERK-pathway is crucial for the function of different immune cells, we postulated an effect on their function and thus interference with anti-tumor immunity. Therefore, we examined the influence of BRAFi/MEKi, either as single agent or in combination, on the maturation of monocyte-derived dendritic cells (moDCs) and their interaction with T cells. DCs matured in the presence of vemurafenib or vemurafenib/cobimetinib altered their cytokine secretion and surface marker expression profile. Upon the antigen-specific stimulation of CD8+ and CD4+ T cells with these DCs or with T2.A1 cells in the presence of BRAFi/MEKi, we detected a lower expression of activation markers on and a lower cytokine secretion by these T cells. However, treatment with any of the inhibitors alone or in combination did not change the avidity of CD8+ T cells in peptide titration assays with T2.A1 cells. T-helper cell/DC interaction is a bi-directional process that normally results in DC activation. Vemurafenib and vemurafenib/cobimetinib completely abolished the helper T-cell-mediated upregulation of CD70, CD80, and CD86 but not CD25 on the DCs. The combination of dabrafenib/trametinib affected DC maturation and activation as well as T-cell activation less than combined vemurafenib/cobimetinib did. Hence, for a potential combination with immunotherapy, our data indicate the superiority of dabrafenib/trametinib treatment.
APA:
Hoyer, S., Eberlein, V., Schuler, G., Berking, C., Heinzerling, L., Schaft, N., & Dörrie, J. (2021). BRAF and MEK Inhibitors Affect Dendritic-Cell Maturation and T-Cell Stimulation. International Journal of Molecular Sciences, 22, 11951. https://doi.org/10.3390/ijms222111951
MLA:
Hoyer, Stefanie, et al. "BRAF and MEK Inhibitors Affect Dendritic-Cell Maturation and T-Cell Stimulation." International Journal of Molecular Sciences 22 (2021): 11951.
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