Project Details
Description
Immunosuppressive mechanisms in the tumor microenvironment promote tumor growth by preventing the
adaptive immune system from mounting effective antitumor responses. One of the main consequences of the
immunosuppressive tumor microenvironment is the induction of tumor antigen-specific T cell tolerance.
Overcoming such blockade has remained a major challenge in cancer immunotherapy. Our data show that
thermic and physical stress induced by low-intensity focused ultrasound (LOFU) prevents the induction of tumor-
antigen specific T cell tolerance and, in combination with ablative therapy, results in improved control of primary
melanoma, reduces local recurrence and markedly decreases the occurrence of pulmonary metastases. This
represents a new therapeutic approach that by acting locally on tumor cells has the potential to inhibit the
establishment of tumor-antigen specific induced T cell tolerance. In this application, our goal is to understand
the mechanisms that induce enhanced immunogenic melanoma cell death after LOFU-treatment, determine the
potential of using LOFU+ablation as an in-situ melanoma vaccine and finally study whether LOFU can increase
efficiency and reduced toxicity when used in combination with checkpoint inhibitors.
Status | Finished |
---|---|
Effective start/end date | 4/1/18 → 3/31/24 |
Funding
- National Cancer Institute: $134,795.00
- National Cancer Institute: $382,013.00
- National Cancer Institute: $374,372.00
- National Cancer Institute: $382,013.00
- National Cancer Institute: $247,218.00
- National Cancer Institute: $370,552.00
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