Cancer cell cycle and adoptive immunotherapy using lymphokine-activated killer cells

The mechanism underlying the lymphokine-activated killer (LAK) cell cytotoxicity to tumor cells in LAK therapy was studied using flow cytometric cell cycle analysis of Daudi cells. It was suggested that the degree of LAK cell cytotoxicity varied depending upon the phase of the cell cycle that the Daudi cells were in: the resting (G0)-phase/preparation for DNA synthesis (G1)-phase, the DNA synthesis (S)-phase or the preparation for mitosis (G2)-phase/mitosis (M)-phase. The levels of expression of intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-3 (LFA-3) and fibronectin (FN), surface antigens playing important roles in LAK cell cytotoxicity, in the different phases of the Daudi cell cycle have been investigated. The level of the expression of ICAM-1 and LFA-3 was significantly higher in S-phase cells and G2/M-phase cells relative to that in G0/G1 phase cells. The level of expression of FN, however, was significantly lower in S-phase cells and G2/M-phase cells in relation to that in G0/G1 phase cells. On the basis of these results, it may be inferred that the degree of LAK cell cytotoxicity is closely related to the cell cycle phase that the Daudi cells are in and the level of expression of surface antigens associated with the cell cycle phase. For Daudi cells treated with cis-diamminedichloroplatinum (II) (CDDP) and mitomycin-c (MMC), the enhancement of the degree of LAK cell cytotoxicity was directly related to the decrease in the proportion of cells in the S-phase. It may be suggested, therefore, that the proportion of cells in the S-phase in a tumor serves as an index of the sensitivity of the tumor cells to LAK cell cytotoxicity, and that designing a therapeutic strategy on the basis of the analysis of tumor cell cycle would help to improve the success of LAK therapy.