Article
Tumour-infiltrating effector T-cells and false-positive identification of tumour progression by MRI and 18FET-PET after dendritic cell vaccination in newly-diagnosed glioblastoma patients
Tumor-infiltrierende Effektor-T-Zellen und falsch-positive Diagnose eines Tumorprogresses im MRT und 18FET-PET nach Vakzinierung mit dendritischen Zellen bei Patienten mit neudiagnostiziertem Glioblastom
Search Medline for
Authors
-
Marion Rapp
- Universitätsklinikum Düsseldorf, Neurochirurgie, Düsseldorf, Deutschland
-
Angeliki Datsi
- Universitätsklinikum Düsseldorf, Institut für Transplantationsdiagnostik und Zelltherapeutika, Düsseldorf, Deutschland
-
Jörg Felsberg
- Universitätsklinikum Düsseldorf, Institut für Neuropathologie, Düsseldorf, Deutschland
-
Norbert Galldiks
- Universitätsklinikum Köln, Neurologie, Köln, Deutschland
-
Marcel Alexander Kamp
- Universitätsklinikum Düsseldorf, Neurochirurgie, Düsseldorf, Deutschland
-
Rüdiger V. Sorg
- Universitätsklinikum Düsseldorf, Institut für Transplantationsdiagnostik und Zelltherapeutika, Düsseldorf, Deutschland
-
Michael Sabel
- Universitätsklinikum Düsseldorf, Neurochirurgie, Düsseldorf, Deutschland
| Published: | June 26, 2020 |
|---|
Outline
Text
Objective: In the phase II GlioVax trial, patients with newly diagnosed glioblastoma are treated with dendritic cell vaccination as add-on to standard radiochemotherapy after fluorescence-guided surgery. Currently, it is not clear, whether dendritic cell vaccination results in effector T cell infiltration of the tumor, whether such infiltrates may mimic tumor progression and whether 18FET-PET imaging may contribute to discriminate progression from an immune response. Therefore, vaccinated 3 patients with suspected tumor recurrence based on MRI have been studied.
Methods: In the event of suspected tumor recurrence based on MRI, vaccinated patients received additional 18FET-PET imaging. When tumor recurrence was confirmed, patients were subjected to surgery and tumor samples assessed histopathologically. In addition, tumor-infiltrating lymphocytes were isolated immunomagnetically and expression of interferon-ɑ as well as transcription factors (T-bet, FoxP3, GATA3) was determined by flow cytometry.
Results: After diagnosed tumor recurrence by MRI, 3 patients received additional 18FET-PET imaging. In 1 patient, it did not confirm recurrence, whereas in 2 of the patients, tumor recurrence was apparently confirmed and patients subjected to surgery. Histopathological examination, however, did not confirm tumor progression, but revealed therapy induced changes. Patients showed high frequencies of CD4+ (40.9/31.9%) and CD8+ (53.6/37.8%) interferon-ɑ producing tumor-infiltrating T cells, which express the transcription factor T-bet, but not FoxP3 or GATA3. In non-vaccinated patients, such cells were present in low frequencies only (1-5%). This indicates that infiltrating TH1 and Tc1 effector T cells are present in the tumor after vaccination.
Conclusion: Dendritic cell vaccination appears to result in a substantial infiltration by interferon-ɑ producing TH1 and Tc1 effector T cells. The presence and activity of these effector T cells may lead to a misinterpretation of MRI (pseudoprogression), which not in all cases can be resolved by additional 18FET-PET imaging.
