Grants and Contracts Details
Description
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.
Status | Finished |
---|---|
Effective start/end date | 1/1/12 → 12/31/17 |
Funding
- National Institute of Allergy and Infectious Diseases: $387,888.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.