Immunomonitoring in glioma immunotherapy: current status and future perspectives

Abstract

Given the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome. Current immunomonitoring assays assess delayed-type hypersensitivity, T-cell proliferation, cytotoxic T-lymphocyte function, cytokine secretion profiles, antibody titers, and lymphocyte phenotypes. Yet, no single immunomonitoring technique can reliably predict outcomes, relegating immunological markers to exploratory endpoints. In response, the most recent immunomonitoring assays are incorporating emerging technologies and novel analysis techniques to approach the goal of identifying a competent immunological biomarker which predicts therapy responsiveness and clinical outcome. This review addresses the current status of immunomonitoring in glioma vaccine clinical trials with emphasis on correlations with clinical response.

Immunotherapy in glioblastoma: emerging options in precision medicine

“…For example, measuring tumor-specific immune responses via various assays for T-cell proliferation, CD4/CD8 cell phenotype, secretion of IFN-γ, cytokine responses of CD8 + T cells and downstream transcription markers have been used in GBM clinical trials [55,[103][104][105][106]. Interpretation of immune-monitoring is primarily restricted to biomarkers that may be surrogate measures [107]. Also, the use of 'liquid biopsies', in which analysis of blood components can provide a real-time comprehensive picture of tumor-associated biomarkers, may have unique applications in tumor diagnostics and monitoring treatment responses [108].…”

A connect-approach in high-grade glioma management; Position statement from the Neuro-Oncology Scientific Club (NOSC), Shiraz, Iran

“…Other alternative chemotherapeutic regimen to consider include the procarbazine, lomustine and vincristine (PCV) combination protocol (Weller et al, 2014) In recurrent GBM setting, some challenging cases who fail to respond to the above, may be enrolled in investigational setups including immunotherapy (PD-1 or IL4 receptor antagonists) (Lamano et al, 2016;Platten, Bunse, Wick, & Bunse, 2016).…”

Issues to Consider in Designing Immunotherapy Clinical Trials for Glioblastoma Management

“…Finding biomarkers to monitor the effectiveness of immunotherapy on GBM disease progression would be very useful, but, thus, far, it appears that only following antibody titers, where the titers increased with greater and longer duration of treatment, is fruitful. Studies examining whether cytokine levels rose in conjunction with administration of dendritic cell vaccines or personalized peptides did not yield statistically significant results [81].…”