Chemoradiation Increases PD-L1 Expression in Certain Melanoma and Glioblastoma Cells

dc.contributor.authorDerer, Anja
dc.contributor.authorSpiljar, Martina
dc.contributor.authorBäumler, Monika
dc.contributor.authorHecht, Markus
dc.contributor.authorFietkau, Rainer
dc.contributor.authorFrey, Benjamin
dc.contributor.authorGaipl, Udo S.
dc.date.accessioned2017-10-10
dc.date.available2017-10-02
dc.date.created2016
dc.date.issued2017-10-10
dc.description.abstractImmunotherapy approaches currently make their way into the clinics to improve the outcome of standard radiochemotherapy (RCT). The programed cell death receptor ligand 1 (PD-L1) is one possible target that, upon blockade, allows T cell-dependent antitumor immune responses to be executed. To date, it is unclear which RCT protocol and which fractionation scheme leads to increased PD-L1 expression and thereby renders blockade of this immune suppressive pathway reasonable. We therefore investigated the impact of radiotherapy (RT), chemotherapy (CT), and RCT on PD-L1 surface expression on tumor cells of tumor entities with differing somatic mutation prevalence. Murine melanoma (B16-F10), glioblastoma (GL261-luc2), and colorectal (CT26) tumor cells were treated with dacarbazine, temozolomide, and a combination of irinotecan, oxaliplatin, and fluorouracil, respectively. Additionally, they were irradiated with a single dose [10 Gray (Gy)] or hypo-fractionated (2 × 5 Gy), respectively, norm-fractionated (5 × 2 Gy) radiation protocols were used. PD-L1 surface and intracellular interferon (IFN)-gamma expression was measured by flow cytometry, and IL-6 release was determined by ELISA. Furthermore, tumor cell death was monitored by AnnexinV-FITC/7-AAD staining. For first in vivo analyses, the B16-F10 mouse melanoma model was chosen. In B16-F10 and GL261-luc2 cells, particularly norm-fractionated and hypo-fractionated radiation led to a significant increase of surface PD-L1, which could not be observed in CT26 cells. Furthermore, PD-L1 expression is more pronounced on vital tumor cells and goes along with increased levels of IFN-gamma in the tumor cells. In melanoma cells CT was the main trigger for IL-6 release, while in glioblastoma cells it was norm-fractionated RT. In vivo, fractionated RT only in combination with dacarbazine induced PD-L1 expression on melanoma cells. Our results suggest a tumor cell-mediated upregulation of PD-L1 expression following in particular chemoradiation that is not only dependent on the somatic mutation prevalence of the tumor entity.en
dc.identifier.citationFrontiers in Immunology 7 (2016). <https://www.frontiersin.org/articles/10.3389/fimmu.2016.00610/full>
dc.identifier.doihttps://doi.org/10.3389/fimmu.2016.00610
dc.identifier.opus-id8846
dc.identifier.urihttps://open.fau.de/handle/openfau/8846
dc.identifier.urnurn:nbn:de:bvb:29-opus4-88469
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/de/deed.de
dc.subjectfractionated radiotherapy
dc.subjectimmunotherapy
dc.subjectcheckpoint inhibitor
dc.subjectPD-L1
dc.subjectIFN-gamma
dc.subjectIL-6
dc.subjectmelanoma
dc.subjectglioblastoma
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleChemoradiation Increases PD-L1 Expression in Certain Melanoma and Glioblastoma Cellsen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleFrontiers in Immunology
local.journal.volume7
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2016
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