Immunotherapies are currently being designed and tested to treat metastatic breast cancer, and the success of any vaccine depends on the immune status of the patient. Although bulky, primary tumors induce tolerance and/or immune suppression, it is not known if surgical removal of primary tumor reverses these conditions and whether or not the levels of metastatic disease after surgery affects tolerance and/or immune suppression. We will assess tolerance and immune suppression in individuals whose primary tumors have been surgically removed but who have metastatic disease. We hypothesize that tolerance and immune suppression are reversed after surgical removal of primary tumor, but they will recur as metastatic disease progresses. However, there will be a """"""""window"""""""" of time after surgery during which individuals will remain immunocompetent and able to respond to their tumor antigens. Using a spontaneously metastatic transplantable tumor, we will test this hypothesis by completing the following aims: (1) determine if the recurrence and/or maintenance of tolerance to tumor-encoded antigens is affected by the progression of metastatic disease; (2) determine if immunosuppressive regulatory T cells and/or plasmacytoid dendritic cells impact the progression of metastatic disease in post-surgery mice; and (3) determine if tolerance to tumor-encoded antigens is reversed by the surgical removal of primary tumor. ? ? ? ?
| Hanson, Erica M; Clements, Virginia K; Sinha, Pratima et al. (2009) Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol 183:937-44 |
