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.
| 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 |
