Grants and Contracts per year
Grants and Contracts Details
The ability of the immune system to successfully attack and eliminate tumors is hindered by the capacity of growing tumors to inhibit the immune response to the tumor. This tumor-mediated inhibition of the immune response not only affects the body's ability to attack the tumor, but also inhibits the ability of physicians to immunize patients against their own tumors, an approach that to date has remained experimental because of this issue. Growing tumors actually have a large number of immune cells within the tumor. However, the functions of these cells are usually inhibited by the tumor cells. Some of these so called "myeloid" immune cells known as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) produce factors which inhibit immune responses against the tumor. Another cell type known as tumor-associated dendritic cells (TADC) normally are good at inducing immune responses to foreign substances, but within a tumor TADCs actually turn off the immune response. If the functions of these tumor-associated immune cells can be altered it may be possible to overcome a significant hindrance to the success of immune-based tumor therapy. It is now known that these innate immune cells, if treated appropriately, have the ability to change their stripes and express functions that inhibit tumor cell growth. One of the internal triggers for this change of function is molecule known as peroxisome proliferator-activated receptor y (PPARy).Our laboratories have produced data that support and extend these findings. We hypothesize that PPARyactivity in tumor-associated myeloid cells maintains these cells in a tumor-supporting role and that elimination of PPARyactivity in myeloid cells will allow for successful immune responsesagainst tumors. Wewill test this hypothesis in two different mouse models of lung cancer in which myeloid cells in the mice do not express PPARyactivity and thus should be able to mount an effective immune responseagainst the tumors.
|Effective start/end date
|2/5/99 → 2/28/12
- National Institute Arthritis Musculoskeletal & Skin
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