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.
Int J Cancer
; 136(8): 1814-26, 2015 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-25242680
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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NF-kappa B
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Vacinas Anticâncer
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Transcriptoma
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Neoplasias Renais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article