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| Item Type: | Article |
|---|---|
| Title: | Gene expression profiling of peripheral blood mononuclear cells during treatment with a gene-modified allogeneic tumor cell vaccine in advanced renal cell cancer: tumor-induced immunosuppression and a possible role for NF-κB |
| Creators Name: | Flörcken, A. and Grau, M. and Wolf, A. and Weilemann, A. and Kopp, J. and Dörken, B. and Blankenstein, T. and Pezzutto, A. and Lenz, P. and Lenz, G. and Westermann, J. |
| Abstract: | Tumor-induced immunosuppression remains a major challenge for immunotherapy of cancer patients. To further elucidate why an allogeneic gene-modified (Interleukin-7(IL-7)/CD80- co-transfected) renal cell cancer vaccine failed to induce clinically relevant TH-1-polarized immune responses, peripheral blood mononuclear cells (PBMCs) from enrolled study patients were analyzed by gene expression profiling (GEP) both prior and after vaccination. At baseline before vaccination, a profound downregulation of gene signatures associated with antigen presentation, immune response/T cells, cytokines/chemokines, and signaling/transcription factors was observed in renal cell cancer patients as compared to healthy controls. Vaccination led to a partial reversion of preexisting immunosuppression, however, GEP indicated that an appropriate TH-1 polarization could not be achieved. Most interestingly, our results suggest that the nuclear factor-kappa B (NF-{kappa}B) signaling pathway might be involved in the impairment of immunological responsiveness and the observed TH-2 deviation. In summary, our data suggest that GEP might be a powerful tool for the prediction of immunosuppression and the monitoring of immune responses within immunotherapy trials. |
| Keywords: | Tumor Vaccination, Renal Cell Cancer, Gene Expression Profiling, Immune Response, NF-{kappa}B |
| Source: | International Journal of Cancer |
| ISSN: | 0020-7136 |
| Publisher: | Wiley-Blackwell |
| Volume: | 136 |
| Number: | 8 |
| Page Range: | 1814-1826 |
| Date: | 15 April 2015 |
| Official Publication: | https://doi.org/10.1002/ijc.29230 |
| PubMed: | View item in PubMed |
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