Protective antitumor activity through dendritic cell immunization is mediated by NK cell as well as CTL activation

Dendritic cells (DCs) are potent professional antigen-presenting cells (APC ) capable of inducing the primary T cell response to antigen. Although tumo r cells express target antigens, they are incapable of stimulating a tumor- specific immune response due to a defect in the costimulatory signal that i s required for optimal activation of T cells. In this work, we describe a n ew approach using tumor-DC coculture to improve the antigen presenting capa city of tumor cells, which does not require a source of tumor-associated an tigen. Immunization of a weakly immunogenic and progressive tumor coculture d with bone marrow-derived DCs generated an effective tumor vaccine. Immuni zation with the cocultured DCs was able to induce complete protective immun ity against tumor challenges and was effective for the induction of tumor-s pecific CTL (cytotoxic T lymphocyte) activity Furthermore, high NK cell act ivity was observed in mice in which tumors were rejected. In addition, immu nization With tumor-pulsed DCs induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture o f DCs with tumors generated antitumor immunity due to the NK cell activatio n as well as tumor-specific T cell. This approach would be useful for desig ning tumor vaccines using DCs when the information about tumor antigens is limited.