Effect of tumor and heparan sulfate on immune responses

Loyola University Chicago, Maywood IL

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Abstract

DESCRIPTION (provided by applicant): 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.