of Interest - Basic Research
Our research focuses on the mechanisms of tumor-mediated
immune suppression in lung cancer. The delineation
of specific immune inhibitory networks in lung cancer
has also led to the development of preclinical models
and clinical trials that utilize this new information
in translational research in genetic immunotherapy.
We have found that non-small cell lung cancer cells
(NSCLC) express type 2 cytokines and potently induce
lymphocyte and macrophage production of the immunosuppressive
cytokine, IL-10. This suppressive network is dependent
upon both expression of cyclooxygenase 2 (COX-2)
and high-level production of PGE2 by NSCLC cells.
We are studying the effect of genetic modulation
of COX-2 in lung cancer. We find that high level
COX-2 expression is responsible for lung tumor invasiveness
and resistance to apoptosis as well as degradation
of cell-mediated immune responses. Additional research
focuses on restoration of antitumor immunity by
introduction of genetically modified antigen presenting
(dendritic) cells at the lung cancer site.
Current projects with Dr.
Michael Roth and Dr.
Don Tashkin focus on toxic mechanisms of marijauana
smoke in the lung which may contribute to pulmonary
disease, especially lung cancer. These mechanisms
include high levels of oxidative stress and impairment
of apoptosis pathways. Most studies utilize in vitro
experimental models and compare marijuana and tobacco
smoke. Studies are also performed on lung cells
obtained from volunteer subjects by bronchiolar
studies with Dr. Wayne Grody focuses on DNA damage
caused by tobacco and marijuana smoke.
>>back to top