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Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

ABSTRACT: 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.

SUBMITTER: Bandyopadhyay S

PROVIDER: S-EPMC4744543 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

Bandyopadhyay Sanmay S Quinn Thomas J TJ Scandiuzzi Lisa L Basu Indranil I Partanen Ari A Tomé Wolfgang A WA Macian Fernando F Guha Chandan C

Journal of immunology (Baltimore, Md. : 1950) 20160111 4

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 the ...[more]

PMID: 26755821

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Project description:BackgroundHigh-intensity focused ultrasound (HIFU) is considered to be an alternative to surgery. Extracorporeal ultrasound-guided HIFU (USgFU) has been clinically used to treat solid tumors. Preliminary trials in a small sample of a Western population suggested that this modality was safe. Most trials are performed in China thereby providing comprehensive data for understanding the safety profile. The aim of this study was to evaluate adverse events of USgFU therapy.Methods and findingsClinical data were searched in 2 Chinese databases. Adverse events of USgFU were summarized and compared with those of magnetic resonance-guided HIFU (MRgFU; for uterine, bone or breast tumor) and transrectal ultrasound-guided HIFU (for prostate cancer or benign prostate hyperplasia). USgFU treatment was performed using 7 types of device. Side effects were evaluated in 13262 cases. There were fewer adverse events in benign lesions than in malignant lesions (11.81% vs. 21.65%, p<0.0001). Rates of adverse events greatly varied between the disease types (0-280%, p<0.0001) and between the applied HIFU devices in both malignant (10.58-44.38%, p<0.0001) and benign lesions (1.67-17.57%, p<0.0001). Chronological analysis did not demonstrate a decrease in the rate of adverse events. Based upon evaluable adverse events, incidences in USgFU were consistent with those in MRgFU or transrectal HIFU. Some side effects frequently occurred following transrectal HIFU were not reported in USgFU. Several events including intrahepatic metastasis, intraoperative high fever, and occlusions of the superior mesenteric artery should be of particular concern because they have not been previously noted. The types of adverse events suggested that they were ultrasonic lesions.ConclusionThe frequency of adverse events depended on the location of the lesion and the type of HIFU device; however, side effects of USgFU were not yet understood. USgFU did not decrease the incidence of adverse events compared with MRgFU.

Dataset Information

Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

Publications

Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

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