Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

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 (U.S.A.)
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

Repository Staff Only: item control page

Open Access
MDC Library