Focused Ultrasound for the Generation of Cancer Immunotherapy

Abstract

Cancer immunotherapies, which seek to arm the patient’s own immune system for personalized therapy, are a promising option for effective elimination of tumors. Focused ultrasound (FUS) is one propitious method for generating anti-tumor immunotherapy, advantageous in its capacity to deliver non-ionizing, non-invasive, tumor-localized treatment; this involves the transdermal deposition of sonic energy at a focal point in the tumor, which induces acute inflammation capable of activating an anti-tumor immune response. Here, we characterize, in vivo, the early (48 hours) adaptive anti-tumor immune responses induced by FUS treatment of tumors. Compared to untreated tumors, tumors treated with mechanical FUS (mFUS) demonstrated increased NF-κB activation in local and distant tumors. Additionally, a “responder” subset of mFUS-treated mice was identified and mFUS-treated tumors exhibited an increased percent of CD4+ T cells and an increased CD4+/CD8+ T cell ratio, as compared to untreated tumors. Immunohistochemical analysis of CD4+ T cells revealed a higher presence of immunostimulatory phenotypes in mFUS-treated tumors compared to untreated tumors. Taken together, these results suggested a FUS-induced shift towards anti-tumor immune activity.