Low-intensity focused ultrasound induces reversal of tumor-induced T cell tolerance and prevents immune escape

Sanmay Bandyopadhyay, Thomas J. Quinn, Lisa Scandiuzzi, Indranil Basu, Ari Partanen, Wolfgang A. Tomé, Fernando Macian, Chandan Guha

Research output: Contribution to journalArticle

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1964-1976
Number of pages13
JournalJournal of Immunology
Volume196
Issue number4
DOIs
StatePublished - Feb 15 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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