Immune therapeutic targeting of glioma cancer stem cells

Abstract

Glioblastoma multiforme (GBM) is a lethal cancer that responds poorly to radiotherapy and chemotherapy. Glioma cancer stem cells (gCSCs) have been shown to recapitulate the characteristic features of GBM and to mediate chemotherapy and radiation resistance. Immunotherapeutic targeting of this cell population holds therapeutic promise but must be considered in the context of the immunosuppressive properties mediated by the gCSC. Recent findings have indicated that this goal will be challenging because the gCSC can suppress both the innate and adaptive immune systems by a variety of gCSC-secreted products and cell-membrane interactions. In this review article, we will attempt to reconcile the disparate research findings regarding the potential of immune targeting of the gCSC and propose several novel solutions.

An experimental study of dendritic cells transfected with cancer stem-like cells RNA against 9L brain tumors

“…Perhaps CSCs may be more capable of immunosuppression sufficient than non-CSCs to allow escape from the host's natural immune surveillance, but this does not necessarily mean that an immune response properly primed by an external therapeutic manipulation will not be able to overcome this immunosuppression and still successfully target and kill these CSCs. 35 In the present study, we found that DCs transfected with 9L CSCs RNA was more effective than other groups, which demonstrated that the strategy may overcome the immunosuppression and induce CTL that target cancer stem cells and prolong the survival of 9L glioma-bearing rats. Although vaccination strategy with dendritic cells loaded with cancer stem cells have been shown to be effective in animal tumor model systems with different cell lines, the mechanism why CSC-targeting DC vaccination generated better antitumor immunity remains unanswered, 30,32 understanding the mechanism would help us to develop more effective cancer immunotherapies.…”

Stem Cell Therapy for Brain Tumors

“…The difficulty in treating GBM seems to be attributable to tumor location, tumor heterogeneity, and the actions of gCSCs in generating and regenerating tumor growth [134]. The BBB, which isolates GBM tumors from the rest of the body, complicates the delivery of therapeutics and reduces immune system access.…”

Engulfing Losers by Winners in Cancer: Do Cancer Stem Cells Catch Eat-me Signals from Noncancer Stem Cells?

“…Development of effective therapies for cancers is a challenging endeavor due to the highly aggressive and therapy-resistant nature of cancer [1,2]. Accumulated evidence suggests that some cancers, such as breast cancer and glioblastoma (GBM) retain steep cellular hierarchy with CSCs at the apex [1,3].…”

“…Accumulated evidence suggests that some cancers, such as breast cancer and glioblastoma (GBM) retain steep cellular hierarchy with CSCs at the apex [1,3]. In these cancers, CSCs, as opposed to other cancer cells, are defined as those that can self-renew, give rise to a broad array of intratumor cell types and drive tumorigenesis.…”