Clinical significance of autologous tumor killing (ATK) activity and its induction therapy in human cancer

The activity of blood lymphocytes to kill autologous freshly isolated tumor cells tested 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 autologous tumor killing (ATK) activity with disease-free interval and total survival indicates that ATK activity is a meaningful prognostic indicator and provides evidence for immunological control of tumor growth and metastasis. Although there is no direct evidence that ATK lymphocytes play a critical role in regression of tumor and prevention of tumor regrowth, the lack of ATK activity in patients who relapsed and died may not result from other factors related to their poor performance status, immune functions and tumor characteristics. Clinical trials with ATK induction therapy resulted in an improvement of the clinical outcome in patients who naturally have no such potential. The data indicate that the presence of both natural and induced ATK activity is strongly associated with long-term survival. In addition, adoptive transfer of BRM-induced ATK effector cells resulted in prolongation of survival time even in patients with documented metastatic tumors. Thus, considerable emphasis should be placed on a strategy that induces ATK activityin vivo. Such an approach may provide a new focus for cancer immunotherapy.Abbreviations ATK Autologous tumor killing - BRM biological response modifiers - AIDS acquired immune deficiency syndrome - NK natural killer - LGL large granular lymphocytes - TIL tumor-infiltrating lymphocytes - MHC major histocompatibility complex - TCR T cell antigen receptor - LAK lymphokine-activated killer - IL Interleukin - IFN interferon - TNF tumor necrosis factor - ATKF autologous tumor killing factor - LFA-1 leukocyte function-associated antigen 1 - ICAM-1 intercellular adhesion molecule 1 - mAb monoclonal antibodies