Biological significance of autologous tumor-killing activity and its induction therapy.

The overall results presented in this review demonstrate that positive ATK activity at the time of surgery predicts a favorable clinical course in patients who have primary localized solid tumor and receive curative operation. The strong correlation of ATK activity with disease-free interval and total survival (a) indicates that ATK activity is a meaningful prognostic indicator and (b) provides evidence for immunological control of tumor growth and metastasis. According to these data, it is unlikely that cancer patients who remain tumor-free after 5 years of follow-up will develop recurrence or die from the disease. Although there is no direct evidence that ATK effector cells play a critical role in regression of tumor and prevention of tumor regrowth, the lack of ATK activity in patients who relapsed and died after surgery may not result from factors related to their poor performance status since no differences have been observed in background factors between ATK-positive and-negative groups. The prognostic value of ATK activity in patients with documented metastatic tumors has not been established yet. In this respect, however, the induction of ATK activity by BRM has positively correlated with prolonged survival time, while such a correlation is not observed with other parameters such as NK cells or LAK cell activity. Based on the possible biological significance of ATK activity, clinical trials have been conducted to determine whether the induction of ATK activity before surgery by administration of BRM could improve the clinical outcome in patients who naturally have no such potential. The preliminary data indicate that the presence of both natural and induced ATK activity is strongly associated with longterm survival. Thus, considerable emphasis should be placed on a strategy that induces ATK activity in vivo. Such an approach may provide a new focus for cancer immunotherapy.