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.
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.
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charité University Medicine, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
authors.forename: Michael
authors.initials: M
authors.lastname: Grau
authors.forename: Annette
authors.initials: A
authors.lastname: Wolf
authors.forename: André
authors.initials: A
authors.lastname: Weilemann
authors.forename: Joachim
authors.initials: J
authors.lastname: Kopp
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Thomas
authors.initials: T
authors.lastname: Blankenstein
authors.forename: Antonio
authors.initials: A
authors.lastname: Pezzutto
authors.forename: Peter
authors.initials: P
authors.lastname: Lenz
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: Jörg
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D059467:Transcriptome / Q000235:genetics* / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D016328:NF-kappa B
keywords: NF-κB; gene expression profiling; immune response; renal cell cancer; tumor vaccination