Cytokine-induced killer (CIK) cells inhibit Plasmodium falciparum parasitemia through cytolytic effector activity in vitro

Cytokine-induced killer (CIK) cells, with dual traits resembling natural killer (NK) and T cells, have shown a promising clinical efficacy against cancer in clinical application leading to licensing of CIK cells in many countries. Here, we demonstrated that CIK cells can also inhibit the growth of Plasmodium falciparum in vitro, leading to a significant reduction in parasitemia levels after 24 h. We found that CIK cells cytotoxicity against infected RBCs is mostly dependent on their secretions rather than cell to cell communication, as they are a substantial repository of lytic agents, including granzyme B, granulysin, as well as perforin. We found that these components in the recombinant form acted synergistically, with granulysin and perforin facilitating granzyme B entry into target cells, resulting in parasite death. Moreover, we observed that priming CIK cells with dendritic cells pulsed with P. falciparum lysate antigen led to diminished CIK cell cytotoxicity against pRBCs. And finally, we found that although combination of CIK cells with chloroquine cannot be synergistic, CIK cells showed a comparable efficacy to chloroquine. Artemisinin combined with effector cells exhibited a slight enhancement in cytotoxicity compared to artemisinin alone. These results propose CIK cells as a potential alternative cell therapeutic approach in the preclinical and clinical setting against malaria and potentially other infections.