title: 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.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461;
authors.forename: Sanmay
authors.identifier: http://orcid.org/0000-0002-1015-2388
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461; and.
authors.forename: Thomas J
authors.identifier: http://orcid.org/0000-0002-5897-8111
authors.initials: TJ
authors.lastname: Quinn
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461; and.
authors.forename: Lisa
authors.initials: L
authors.lastname: Scandiuzzi
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461; and.
authors.forename: Indranil
authors.identifier: http://orcid.org/0000-0003-1057-8888
authors.initials: I
authors.lastname: Basu
authors.affiliation: Philips Healthcare, Bethesda, MD 20817.
authors.forename: Ari
authors.initials: A
authors.lastname: Partanen
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461; and.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tomé
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461; Philips Healthcare, Bethesda, MD 20817 cguha@montefiore.org fernando.macian@einstein.yu.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Macian
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY 10461; and Philips Healthcare, Bethesda, MD 20817 cguha@montefiore.org fernando.macian@einstein.yu.edu.
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000473:pathology / Q000628:therapy; D011878:Radiotherapy; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*; D014464:Ultrasonic Therapy / Q000379:methods*