Understanding the immune dysfunctions induced by cancers will help in development of effective therapeutic approaches. In cancer, CD4+T have been shown to be skewed toward Th2 responses. Optimal activation and polarization of resting CD4 + cells, depends upon antigen recognition in association with antigen presenting cells (APC). Another factor in the immune response is the basement membrane. Through its actions on APCs, heparan sulfate, a component of the basement membrane, has been suggested to skew the immune response to a Thl response. We hypothesize that the polarized Th2 immune response in cancer that is due to polarized or defective APC that can be corrected by treatment with heparan sulfate.
Aim #1 will determine if T cells are skewed to a Th2 response and/or sub-optimally activated in LLC-bearing mice and if this is due to Th2-polarized or sub-optimally activated APC. Also determined will be if the macrophage and/or the dendritic cell is the APC population responsible for the immunological defects and T cell skewing in LLC-bearing mice.
Aim #2 will determine if T cell skewing in LLC-bearing mice can be overcome by treatment of antigen-presenting macrophages, dendritic cells, or both, with the basement membrane component, heparan sulfate.
Aim #3 will determine if in vivo heparan sulfate treatment of LLC-bearing mice can increase the Th1 response. Results of our studies will lead to more effective immunotherapeutic approaches for cancer treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA103768-04
Application #
7122859
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (29))
Program Officer
Bini, Alessandra M
Project Start
2003-09-01
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$48,678
Indirect Cost
Name
Loyola University Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Rashid, Rashid M; Lee, John M; Fareed, Jawed et al. (2007) In vitro heparan sulfate modulates the immune responses of normal and tumor-bearing mice. Immunol Invest 36:183-201
Rashid, Rashid M; Lee, John M; Fareed, Jawed et al. (2006) In vivo heparan sulfate treatment alters the immune response of normal and LLC-bearing mice. Immunopharmacol Immunotoxicol 28:67-79
Rashid, Rashid M; Achille, Nicholas J; Lee, John M et al. (2005) Decreased T-cell proliferation and skewed immune responses in LLC-bearing mice. J Environ Pathol Toxicol Oncol 24:175-92