Low-Intensity Focused Ultrasound Induces Reversal of
Tumor-Induced T Cell Tolerance and Prevents Immune Escape. Bandyopadhyay, Quinn,
Scandiuzzi, et al. J Immunol. 2016. Jan 11.
Immune responses against cancer cells are often
hindered by immunosuppressive mechanisms that are developed in the tumor
microenvironment. Induction of a hyporesponsive state in tumor Ag-specific T
cells is one of the major events responsible for the inability of the adaptive
immune system to mount an efficient antitumor response and frequently
contributes to lessen the efficacy of immunotherapeutic approaches. Treatment
of localized tumors by focused ultrasound (FUS) is a minimally invasive therapy
that uses a range of input energy for in situ tumor ablation through the
generation of thermal and cavitation effect. Using a murine B16 melanoma tumor
model, we show that a variant of FUS that delivers a reduced level of energy at
the focal point and generates mild mechanical and thermal stress in target
cells has the ability to increase immunogenic presentation of tumor Ags, which
results in reversal of tumor-induced T cell tolerance. Furthermore, we show
that the combination of nonablative low-energy FUS with an ablative
hypofractionated radiation therapy results in synergistic control of primary
tumors and leads to a dramatic reduction in spontaneous pulmonary metastases
while prolonging recurrence-free survival only in immunocompetent mice.
This one has a long way to go...but hey! If it works in mice...maybe it will work in ratties, too! - c
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