Role of tumor cell apoptosis in tumor antigen migration to the draining lymph nodes

Establishment of an immune response against cancer may depend on the capaci ty of dendritic cells to transfer tumor Ags into T cell-rich areas. To chec k this possibility, we used a colon cancer cell variant that yields tumors undergoing complete T cell-dependent rejection when injected into syngeneic rats. We previously demonstrated that immunogenicity of these tumors depen ded on the early apoptosis of a part of these tumor cells. In this paper we show that fluorescent tumor cell proteins are released from FITC-labeled t umor cells and undergo engulfment by tumor-infiltrating monocytes without a phenotype of mature dendritic cells or macrophages. Fluorescence-labeled m ononuclear cells with a phenotype of MHC class II+ dendritic cells are also found in the T cell areas of the draining lymph nodes. Interestingly, no f luorescent cell can be found in lymph nodes after a s,c, injection of Bcl2- transfected apoptosis-resistant tumor cells that yielded progressive tumors , Proliferation of tumor-immune T lymphocytes was induced by dendritic cell s isolated from the draining lymph nodes recovered after a s,c, injection o f apoptosis-sensitive, but not apoptosis-resistant, tumor cells. These resu lts show that tumor cell apoptosis releases proteins that are engulfed by i nflammatory cells in the tumor, then transported to lymph node T cell areas where they can induce a specific immune response leading to tumor rejectio n.