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- 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-κ B.
- Authors
Flörcken, Anne; Grau, Michael; Wolf, Annette; Weilemann, André; Kopp, Joachim; Dörken, Bernd; Blankenstein, Thomas; Pezzutto, Antonio; Lenz, Peter; Lenz, Georg; Westermann, Jörg
- 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-cotransfected] renal cell cancer (RCC) vaccine failed to induce clinically relevant TH-1-polarized immune responses, peripheral blood mononuclear cells 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 RCC 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 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.
- Publication
International Journal of Cancer, 2015, Vol 136, Issue 8, p1814
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.29230