Title:Approaches to Improve Efficiency of Dendritic Cell-based Therapy of High Grade Gliomas
Volume: 22
Issue: 37
Author(s): Dimitry A. Chistiakov, Ivan V. Chekhonin, Olga I. Gurina, Yuri V. Bobryshev and Vladimir P. Chekhonin
Affiliation:
Keywords:
Glioblastoma, dendritic cell vaccine, immune therapy, antigenic peptide, immune suppression, dendritic cell maturation.
Abstract: High grade gliomas (HGGs) are the most frequent and highly invasive type of
brain tumors, which arise from glial cells. Among HGGs, glioblastoma multiforme (GBM)
is the commonest and deadliest tumor type. Standard HGG therapy that involves tumor
resection followed by concomitant treatment with radiation exposure and temozolomide
(TMZ) cannot prevent recurrent tumor. The median survival of treated patients after surgery
does not exceed 1.5 years. Vaccination with autologous dendritic cells (DCs) pulsed with
tumor-specific peptides, antigens, or lysates is considered as a promising option to induce a
potent anti-tumor immune response and cytotoxicity against GBM cells. However, since the
tumor microenvironment is highly immunosuppressive and immunotolerant, specialized
approaches should be applied to protect DC transplants against tumor-induced functional
impairment and inhibition. So far, many phase I-III clinical trials utilizing DC vaccines for
HGG treatment were completed or are underway. In summary, DC vaccination was safe and
well tolerated by patients. DC-induced anti-tumor immune responses correlated with prolonged overall and progression-
free survival. Combination of DC therapy with other interventional strategies (i.e., radiotherapy, chemotherapy,
antibodies, etc.) and multimodal approaches should improve HGG treatment outcomes. In this review,
we consider strategies that provide an option to override the immune inhibitory tumor microenvironment and
boost DC vaccine-based antitumor immune response.