Lung cancer remains the major cancer-related cause of death in the Western World and intense efforts are directed toward the development of adjuvant therapy for the treatment of this disease. While immunotherapy targeting the adaptive immune response in the form of T lymphocytes has been successful for several solid tumors, such as melanoma and prostate cancer, it has been extremely unsuccessful in lung cancer. We have recently discovered that, unlike other solid tumors, the innate rather than adaptive immune system plays a critical role in immunosurveillance for lung cancer. Furthermore, individual differences in natural killer cells (NK cells) play a role in susceptibility or resistance to this disease. In this proposal we focus on the role of natural killer cells in immunosurveillance and immunotherapy of lung cancer. We plan to explore mechanistic aspects of lung cancer immunosurveillance in a mouse model and will evaluate the immunologic basis of human susceptibility to this disease. In the first aim we will study the role of the activating receptor NKp46 in lung cancer-specific activation of NK cells. In the second aim we will evaluate the mechanisms used by NK cells to control lung cancer in vivo and in the third aim we will focus on the inhibitory receptor Ly49C as it relates to strain-specific differences in anti-cancer activity of NK cells. In the fourth and final aim we plan to evaluate the licensing status of human NK cells and susceptibility to lung cancer. 1

Public Health Relevance

It is currently unknown how the immune system controls the development and growth of lung cancer. This grant application explores the immunologic basis for susceptibility to lung cancer, focusing on a population of cells known as natural killer cells. Results from this application coul improve our understanding of immunosurveillance for lung cancer and immunotherapy for this disease.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01BX002299-01
Application #
8629870
Study Section
Oncology B (ONCB)
Project Start
2014-01-01
Project End
2017-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
St. Louis VA Medical Center
Department
Type
DUNS #
033986766
City
St. Louis
State
MO
Country
United States
Zip Code
63106