Related Experiment Video
Updated: Aug 9, 2026
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 8, 2019
Characterization of gene expression profiles of T cells during anti-tumor response
Christian Stremmel1, Renate Siebenhaar, Roland Croner
1Department of Surgery, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany. Stremmel@ch11.ukl.uni-freiburg.de
Background And Aims:
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.
Conclusion:
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.
Insights
Tumor cells cause T cell immune dysfunction, allowing cancer to evade detection. Microarray analysis identified specific gene expression profiles in dysfunctional T cells, revealing subtle changes linked to distinct in vivo behaviors.
Area of Science:
- Immunology
- Genomics
- Cancer Research
Background:
- Tumor cells often induce T cell dysfunction, enabling immune evasion.
- Identifying these dysfunctional T cells is crucial for understanding anti-tumor immunity.
Purpose of the Study:
- To investigate the genomic expression profile of T cells in tumor-bearing hosts.
- To identify molecular markers of T cell dysfunction in anti-tumor responses.
Main Methods:
- EL4 thymoma cells were engineered to express costimulatory ligands (B7-1, B7-2).
- Oligonucleotide-based DNA chip microarrays were employed to analyze T cell gene expression.
- Standard assays like ELISA and FACS were used for comparative analysis.
Main Results:
- Functional differences in T cells against tumor cells were not discernible via standard methods (FACS, ELISA).
- Microarray analysis successfully identified differentially expressed genes in T cells unable to reject tumors.
- Gene expression changes were observed in pathways regulating innate immune responses, not Th1/Th2 cytokines.
Conclusions:
- The "gene profile" of T cells can serve as a biomarker for anti-tumor responses.
- Genomic-scale analysis reveals subtle gene expression changes indicative of distinct T cell behavior in vivo.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:27Tumor Immunotherapy