Characterization of gene expression profiles of T cells during anti-tumor response.
OBJECTIVE
T cells of tumor-bearing mice or cancer patients exhibit an immune dysfunction, enabling the tumor to escape immune surveillance.


METHODS
The experiments are based on EL4 thymoma cells that were transfected with costimulatory ligands B7-1, B7-2, or both at the same time. We used oligonucleotide-based DNA chip microarrays to characterize the genomic expression profile of peripheral T cells according to their anti-tumor immune response in vivo. These murine T cells were also characterized by ELISA, FACS analysis, and co-stimulatory assays.


RESULTS
Using commonly established methods, such as FACS analysis or the analysis of the cytokine profile by ELISA, it was not possible to determine functional differences in the in vivo activity of T lymphocytes against tumor cells. EL4 tumor cells induced multiple anti-tumor immune responses in vivo depending on their B7 expression. We successfully used microarray analysis to identify genes that were differentially expressed in the dysfunctional T cells, which were unable to reject tumors in vivo. Although Th1 and Th2 cytokine expression was not affected, we observed differential expression of genes involved in the regulation of an innate immune response.


CONCLUSIONS
Our results provide evidence that the anti-tumor response can be identified by the "gene profile" of T cells. Genomic scale analysis offers the opportunity to identify subtle changes in gene expression in T cells reflecting a distinct biological behavior in vivo.
Stremmel
Christian
C
Department of Surgery, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany. Stremmel@ch11.ukl.uni-freiburg.de
Siebenhaar
Renate
R
Croner
Roland
R
Reingruber
Bertram
B
Slavin
Anthony J
AJ
Hohenberger
Werner
W
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004273:DNA, Neoplasm / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D004273:DNA, Neoplasm