Maturation of cytotoxic T lymphocytes against a B7-transfected nonmetastatic tumor: a critical role for costimulation by B7 on both tumor and host antigen-presenting cells

It is generally believed that CTLs mature in lymphoid organs and then migrate into target tissues to execute their effector functions. This notion, however, is based on studies using antigens that are readily localized in the lymphoid tissue, such as viruses and allogeneic transplants. The site for maturation of CTLs for nonmetastatic tumors has not been determined. Because nonmetastatic tumor cells are not localized in lymphoid tissues, it is questionable whether such tumors are efficient inducers of antitumor CTLs. Here, we report that a nonmetastatic B7+ plasmacytoma induces strong effector CTL response. Thus, it is possible to induce CTLs with strong ex vivo CTL activity in the absence of tumor metastasis. In addition, a detailed kinetic analysis of CD8 T cell recruitment and maturation of CTL activity suggests that antitumor CTLs mature within the tumor rather than in the lymphoid tissues. Interestingly, despite B7-1 expression on tumor cells, induction of effector CTLs also requires costimulation by B7 on host antigen-presenting cells. These findings have important implications for tumor gene therapy and for understanding the mechanism of CTL induction in vivo.