Abstract
Abrogating the suppression of glioma-infiltrating Tregs in the periphery and the central nervous system is essential to successful glioma rejection. We sought to improve the immune response in glioma-bearing mice, by investigating new strategies using the anti-CD25 immunotherapy. We found a complete long-term survival of glioma-bearing mice treated with a combination of systemic and intracranial anti-CD25 mAb immunotherapy as compared to systemic administration of anti-CD25 mAb. In addition, the group of mice that had been cured by the combined anti-CD25 mAb showed long-term survival without late tumor relapse when challenged with the GL261 glioma. The antitumor immune response was investigated by analysis of antitumor immune response (CTL). Results showed that the use of the combined injections of anti-CD25 mAb induced efficient targeting of Tregs expansion inside and outside of the brain and altered Tregs trafficking in the bone marrow and brain areas where antitumor immunity was primed.
Highlights
Glioblastoma tumors are characterized by extensive microvascular infiltration and rapid proliferation
We analyzed the effect of the glioma on the expansion of the populations of CD4+ and CD8+ T cells as well as Tregs in the bone marrow of glioma-bearing mice at three weeks after tumor implantation
The intracellular expression of Foxp3 in gated CD4+ T cells from the bone marrow of glioma-bearing mice confirmed the presence of Tregs in 20.0%± 2.33% of the cells
Summary
Glioblastoma tumors are characterized by extensive microvascular infiltration and rapid proliferation. Targeting tumor infiltrating lymphocytes (TIL) as well as regulatory T cells (Tregs) can completely destroy established solid tumors by favoring antitumor immune responses. An active suppression by Tregs plays an important role in the downregulation of T cell responses to foreign and self-antigens in the peripheral immune system. Convincing data regarding the role of Tregs in tumors of the central nervous system (CNS) have been accumulating only during the last few years. Efforts aimed at developing new therapies have focused on strategies that target tumor cells while sparing normal cells. One such approach, immunotherapy, has shown promises within the spectrum of agents used against malignant brain tumors
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