Systemic immune derangements are shared across various CNS pathologies and reflect novel mechanisms of immune privilege

Abstract

The nervous and immune systems interact in a reciprocal manner, both under physiologic and pathologic conditions. Literature spanning various CNS pathologies including brain tumors, stroke, traumatic brain injury and de-myelinating diseases describes a number of associated systemic immunologic changes, particularly in the T-cell compartment. These immunologic changes include severe T-cell lymphopenia, lymphoid organ contraction, and T-cell sequestration within the bone marrow. In this review, we propose that the same immunologic changes in the T-cell compartment, hereafter termed ‘systemic immune derangements’, are present across CNS pathologies and may represent a novel, systemic mechanism of immune privilege for the CNS. We further demonstrate that systemic immune derangements are transient when associated with isolated insults such as stroke and TBI but persist in the setting of chronic CNS insults such as brain tumors. Systemic immune derangements have vast implications for informed treatment modalities and outcomes of various neurologic pathologies.

Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults

“…A proportion of T cells infiltrating brain tumors are immunosuppressive regulatory T cells, that actively suppress the function of antitumor T cells [158]. A level of dysfunction, potentially specific to brain tumors, is that of T cell sequestration and peripheral immune dysfunction, which may represent a mechanism of CNS-mediated immunosuppression [159][160][161]. Further studies are needed to define and overcome glioma specific routes of T cell dysfunction.…”