Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme

Abstract

Glioblastoma Multiforme (GBM, Astrocytoma grade-IV) is the most common primary malignant brain tumour in adults and unfortunately the most deadly. Patients with GBM exhibit a deficient anti-tumor immune response. Immunotherapy is rapidly becoming one of the pillars of anti-cancer therapy. GBM has not received similar clinical successes as of yet, a fact which may be attributed to its relative inaccessibility,its poor immunogenicity, or any of the many other immune mechanisms known to be inactivated in these tumor cells. Focused Ultrasound (FUS) is emerging as a promising treatment approach. The effects of FUS on the tissue are not merely thermal. Reported FUS-induced acoustic cavitation which carries both mechanical and molecular implications as well as FUS induced immunomodulation play important roles. This is a concise research highlights on a comprehensive report by the same group. We separately discuss the different pertinent immunosuppressive mechanisms harnessed by GBM and the immunomodulatory effects of FUS. The three modes of FUS action can all be assigned a molecular final common pathway of immunomodulation. Thermal ablation induced immune effects, microbubbles effects in disrupting the BBB and introducing antigens and drugs to the tumor milieu as well as FUS induced molecular effects are discussed. The effect of FUS on the pro-inflammatory cytokines secretion profile, the stress response, the intra-tumoral immune-cellspopulations, dendritic cells activitymoderation and FUS induced increased cytotoxic cells potency are all discussed. A conceptual synopsis of the synergistic treatment of GBM utilizing FUS and immunotherapy is presented. The interaction of multiple approaches harnessing immune-components and circumventing immunosuppressing mechanisms may herald a new era in the fight against GBM.