Modulations in the Peripheral Immune System of Glioblastoma Patient Is Connected to Therapy and Tumor Progression—A Case Report from the IMMO-GLIO-01 Trial

Abstract

Immune responses are important for efficient tumor elimination, also in immune privileged organs such as the brain. Fostering antitumor immunity has therefore become an important challenge in cancer therapy. This cannot only be achieved by immunotherapies as already standard treatments such as radiotherapy and chemotherapy modify the immune system. Consequently, the understanding of how the tumor, the tumor microenvironment, and immune system are modulated by cancer therapy is required for prognosis, prediction, and therapy adaption. The prospective, explorative, and observational IMMO-GLIO-01 trial was initiated to examine the detailed immune status and its modulation of about 50 patients suffering from primary glioblastoma multiforme (GBM) or anaplastic astrocytoma during standard therapy. Prior to the study, a flow cytometry-based assay was established allowing the analysis of 34 immune cell subsets and their activation state. Here, we present the case of the first and longest accompanied patient, a 53-year-old woman suffering from GBM in the front left lobe. In context of tumor progression and therapy, we describe the modulation of the peripheral immune status over 17 months. Distinct immune modulations that were connected to therapy response or tumor progression were identified. Inter alia, a shift of CD4:CD8 ratio was observed that correlated with tumor progression. Twice we observed a unique composition of peripheral immune cells that correlated with tumor progression. Thus, following up these immune modulations in a closely-meshed manner is of high prognostic and predictive relevance for supporting personalized therapy and increasing therapy success.Clinical Trial registration: , identifier NCT02022384 (registered retrospectively on 13th of December, 2013).

Temporal and spatial modulation of the tumor and systemic immune response in the murine Gl261 glioma model

“…Early data from the IMMO-GLIO-01 glioma clinical trial which tracks the immune response during treatment regimens demonstrates the value of such information. In a case study, RT treatment coincided with declines in T cells, B cells, pDCs and NK cells, and a shift of the CD4:CD8 ratio correlated with MRI tumor recurrence offering some hope in the identification of treatment response or prognostic indicators [6]. In the move toward personalized medicine, tracking of the patient immune response before, during and after treatment and with different treatment combinations will give greater understanding of when and what therapy should be administered at each time point to induce/maintain a state of tumor stabilization/elimination.…”

“…This has precedence. The IMMO-GLIO-01 glioma clinical trial published a case study of a 53-year old women with GBM in which longitudinal monitoring of her immune response during the treatment regimen, noted that a shift of the CD4:CD8 ratio was associated with magnetic resonance imaging (MRI) tumor progression [6].…”

Value of 18F-FET PET in Patients With Suspected Tumefactive Demyelinating Disease—Preliminary Experience From a Retrospective Analysis

“…On the other hand, a functioning immune system is important for the response to tumors, and immunosuppression was shown to affect the prognosis in glioblastoma patients. 48,49 We acknowledge several limitations of our study. First, we only included patients where the MR scan was equivocal, and can thus not comment on the diagnostic accuracy of MR vs. FET-PET imaging in a more general population of patients with demyelinating disease.…”

Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System

“…Yet, little is known about how radiation impacts on immune cells even though they are present in the tumor and its microenvironment as well as in inflamed and degenerated areas. Detailed immunophenotyping is increasingly being applied for definition of prognostic and predictive markers for inflammatory and cancer diseases [ 9 , 10 , 11 ]. However, it has to be taken into account that RT might not only result in immune activation but also in immune suppression (summarized in Reference [ 12 ]).…”