Comparative gene expression profiling of cytokine-induced killer cells in response to acute myloid leukemic and acute lymphoblastic leukemic stimulators using oligonucleotide arrays.
OBJECTIVE
To study the molecular cytolytic mechanism of CD3+CD56+ cytokine-induced killer (CIK) effector cells, especially with reference to their ability to deliver potent cytolytic activities against acute myeloid leukemic (AML), but not acute lymphoblastic leukemic (ALL), blasts.


METHODS
We employed Affymetrix (Santa Clara, CA, USA) oligonucleotide arrays to compare the gene expression profiles of CIK cells before and after stimulation by different leukemic cells. This includes the generation of six independent sets of CIK effectors against AML and ALL leukemic targets.


RESULTS
Majority of the highly expressed genes of the various CD3+CD56+ CIK effectors were regulated in concordance with, and were consistent with, a Th1 and Tc1 polarization. Genes related to protein synthesis were highly expressed in CIK cells, and upon stimulation by leukemic targets, genes related to signaling, immune responses, and transcription were further upregulated. More importantly, and corroborated with their cytolytic activities, the NK receptors genes, NKG2C and NKG2E, together with perforin, were upregulated exclusively in CIK cells that were cytolytic to susceptible AML targets. In comparison, transforming growth factorbeta1, a cytokine with immune inhibitory function, was exclusively upregulated in CIK cells that were exposed to resistant ALL targets.


CONCLUSIONS
In addition to demonstrating the presence of molecular regulatory pathways that are common to CIK effector cells, our present study also reveals molecular events that are unique to CIK effectors on stimulation with cytolytic-susceptible (AML) or cytolytic-resistant (ALL) targets. These observations could allow the design of strategies for future research on the application of CIK effector cells for cancer immunotherapy.
Linn
Yeh Ching
YC
Department of Hematology, Singapore General Hospital, Singapore.
Wang
Suk Mei
SM
Hui
Kam M
KM
D000208:Acute Disease; D016207:Cytokines / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*
D016207:Cytokines