Immunotherapeutic Treatment Strategies for Primary Brain Tumors

Abstract

Primary brain tumors account for a minor fraction of cancer diagnoses made worldwide and remain one of the most difficult to treat. Despite ongoing efforts to improve the quality of life and overall survival of these patients, current multimodality therapy has achieved only modest gains; the median survival is approximately 14 months among patients with the deadliest form of primary brain tumor, glioblastoma multiforme. Although the brain has been long considered an immunologically privileged organ, there is increased awareness of and appreciation for the complex interplay between the nervous system and the immune system in the setting of many disease states, including neoplastic. Although the concept of harnessing the specificity, activity, and memory of the immune system toward the treatment of brain tumors has been in existence for several decades and the neuro-oncology literature holds many publications that once promised of a breakthrough, only recently has a strategy emerged that addresses many of the limitations identified through past failures. It is with cautious optimism that the authors review the past and discuss the present status of immunotherapy and its role in the management of patients with primary brain tumors.

Genetic and Immunology of Brain Tumors

“…In gliomas, T cells, specifically the CD41 population, both in peripheral blood and in the tumor microenvironment, have depressed function . Innate helper T cells (CD41) reveal weak proliferative responses and dramatically lowered synthesis of the TH1 cytokine IL-2 (Das et al, 2008). One hypothesis sugested that these are actually resident T cells passively infiltrating the tumor across a compromised BBB caused by the tumor; alternatively, they may represent a population that once was active but has been subsequently rendered inactive by the host of immunosuppressive mechanisms found in the tumor microenvironment (Han et al, 2010).…”

“…Cytokine production acts as a means of communication in the tumor microenvironment (Giezeman-Smits et al, 2000). Several strategies for delivery of cytokines to the CNS have been studied, including injection/infusion of recombinant cytokines, vectors containing cytokine encoding genes, cells that secrete cytokines, or cytokines linked to toxins (Das et al, 2008).…”

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part 1: stimulatory effects on blood monocytes and monocyte-derived cells of the brain

“…Emphasis has been placed on the possibility of enhancing activity of antigen presenting cells (APC) by manipulating the processing of tumor-specific antigens, which should ultimately lead to an improvement in the specific killing of tumor cells while sparing normal tissue 1–5…”

Human glioma cell culture: two FCS-free media could be recommended for clinical use in immunotherapy

“…One therapy emerging over the last few years is active immunotherapy to initiate T-cell-mediated antitumour immunity (Delhaye et al 2003;Carpentier and Meng 2006;Das et al 2008;Yamanaka 2008). This strategy requires the administration of an antigenic target.…”