Abstract
Glioblastoma (GBM) is an aggressive brain tumor with a dismal prognosis. Salvage neurosurgical resection is performed if possible and GBM patients are hereafter treated with Stupp’s regime as standard treatment in the
primary setting. However, after relapse, treatment in the recurrent setting
shows very limited effect. We are monitoring the immune system of patients
participating in a phase II clinical trial, where patients with recurrent GBM
receive Nivolumab and Bevacizumab, treatments blocking PD1 and VEGF,
respectively. The clinical trial consists of two arms. Arm A includes patients
where surgical removal of the tumor is possible, and arm B includes patients who are only able to receive medical treatment. Arm A has received
Nivolumab 7 days prior to surgery. Single cells suspension was produced
from the resected tumors and blood samples was collected from patients
through the course of treatment, wherefrom PBMCs (peripheral blood
mononuclear cells) were purified. All samples were immunophenotyped
using multi-color flow cytometry, to identify and follow the distribution of
various immune cell types, and determine their expression of activating and
inhibitory molecules over the course of treatment, in the periphery and in
the tumor. An activated subset of T cells was characterized by CD103 (tissue
residence), CD39 (antigen exposure) and CD69 (cytotoxicity). Such T cell
populations were significantly enriched in the tumor. Importantly, we could
demonstrate the presence of Nivolumab in the tumor, using an anti-IgG4
antibody to detect Nivolumab binding to T cells. We observed IgG4 positive T cell in the tumor digest, suggesting T cells binding Nivolumab are
present in the tumor. Additional data analysis will be performed prior to
the conference. With this we hope to gain further knowledge of the immune
system’s role in tumor clearance in the brain and the impact of immunotherapy hereupon.
primary setting. However, after relapse, treatment in the recurrent setting
shows very limited effect. We are monitoring the immune system of patients
participating in a phase II clinical trial, where patients with recurrent GBM
receive Nivolumab and Bevacizumab, treatments blocking PD1 and VEGF,
respectively. The clinical trial consists of two arms. Arm A includes patients
where surgical removal of the tumor is possible, and arm B includes patients who are only able to receive medical treatment. Arm A has received
Nivolumab 7 days prior to surgery. Single cells suspension was produced
from the resected tumors and blood samples was collected from patients
through the course of treatment, wherefrom PBMCs (peripheral blood
mononuclear cells) were purified. All samples were immunophenotyped
using multi-color flow cytometry, to identify and follow the distribution of
various immune cell types, and determine their expression of activating and
inhibitory molecules over the course of treatment, in the periphery and in
the tumor. An activated subset of T cells was characterized by CD103 (tissue
residence), CD39 (antigen exposure) and CD69 (cytotoxicity). Such T cell
populations were significantly enriched in the tumor. Importantly, we could
demonstrate the presence of Nivolumab in the tumor, using an anti-IgG4
antibody to detect Nivolumab binding to T cells. We observed IgG4 positive T cell in the tumor digest, suggesting T cells binding Nivolumab are
present in the tumor. Additional data analysis will be performed prior to
the conference. With this we hope to gain further knowledge of the immune
system’s role in tumor clearance in the brain and the impact of immunotherapy hereupon.
| Original language | English |
|---|---|
| Article number | CTIM-23 |
| Journal | Neuro-Oncology |
| Volume | 23 |
| Issue number | Supplement_6 |
| Pages (from-to) | vi55-vi55 |
| ISSN | 1522-8517 |
| DOIs | |
| Publication status | Published - 2021 |