The effect of pretreatment with chemotherapeutic drugs on the susceptibility to lymphokine activated CD8+ T lymphocyte-mediated cytotoxicity in CMK leukemia cells

Objectives: Certain tumor cells pretreated with chemotherapeutic drugs become more susceptible to death by apoptosis induced by killer cells of the immune system. We examined the CD8+ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity in myeloid leukemia cell lines pretreated with chemotherapeutic drugs. Methods: Peripheral blood mononuclear cells were expanded in vitro in the presence of phytohemagglutinin-P, interleukins-2 and -15. CD3+ CD8+ cells representing the CTLs were isolated using magnetic immunoselection and used in immune cytotoxicity experiments against K562 and CMK leukemia cells, pretreated with two different concentrations of cytarabine and etoposide. Results: In CMK cells pretreated with etoposide at 2 μM and 20 μM concentrations, the mean cell-mediated immune cytotoxicity rose to 21.4 ± 12.9% (p=0.09) and 23.4 ± 12.6% (p=0.046), respectively, when compared to the control value of 6.6 ± 3.8%. In CMK cells pretreated with cytarabine at 1 μM and 10 μM concentrations, the mean immune cytotoxicity rose to 14.3 ± 11.2% and 22.6 ± 15.2%, respectively, compared to the control value of 8.7 ± 6.3%, although these results did not reach statistical significance. However, a similar increase in CTL-mediated immune cytotoxicity was not observed against drug-treated K562 cells. Conclusion: This study suggests that pretreatment with chemotherapeutic drugs can render CMK leukemia cells more susceptible to immune attack by activated CTLs. Further studies are needed to explore this phenomenon, to establish an immune-enhancing effect of pretreatment with chemotherapy in the treatment of leukemia.