| The recognition and destruction of cancerous cells by the immune system is a complex process that requires cellular communication via cytokines as well as cell-to-cell receptor-mediated interactions. Two very important aspects of antitumor immunotherapy are initiating antitumor cellular immune responses and increasing the tumor's sensitivity to the host's antitumor immunity. To initiate cellular antitumor immunity, orchestrating the interaction between antigen presenting cells (APCs) and immune effector cells, such as T cells and NK cells, is necessary. The migration of APCs, such as dendritic cells (DCs), and immune effector cells is controlled by chemokines. Administration of chemokines is a strategy to induce the colocalization of APCs and immune effector cells and initiate anti-tumor immunity. One of the mechanisms by which a tumor can evade host anti-tumor immunosurveillance is by affecting the expression of cell surface MHC class I and II molecules on the tumor cell surface. Understanding the normal mechanisms regulating cell surface expression of MHC molecules on tumors and finding novel approaches to control the expression of MHC molecules on tumors can also contribute to the fight against cancer.;As described in this dissertation, utilizing a murine mammary cancer model, I have shown that intratumoral administration of CCL21 and CCL19 delivered in a sustained release system (Hydron) inhibits mammary tumor growth. The antitumor effect of intratumoral administration of CCL21-Hydron is related to the attraction of lymphoid DCs and CD84 T cells to the tumor site. In addition, in my studies, the interactions and functions of two proteins, invariant chain (Ii) and amyloid precursor-like protein 2 (APLP2), have been investigated in regard to the regulation of cell surface expression of MHC molecules on human breast cancer cell lines. Ii alters the cell surface expression and the stability of the MHC class I molecule on breast cancer cells. APLP2 interacts with Ii, and APLP2 influences the cleavage of Ii and the binding of Ii to MHC class II molecules. Overall, these findings provide a novel immunotherapeutic strategy to treat breast cancer and progress toward further understanding of presentation of breast cancer antigens. |
