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

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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., Grau, M., Wolf, A., Weilemann, A., Kopp, J., Dörken, B., Blankenstein, T., Pezzutto, A., Lenz, P., 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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