Tumor endothelial marker 8 expression levels in dendritic cell-based cancer vaccines are related to clinical outcome

Franco Maria Venanzi, Massimiliano Petrini, Laura Fiammenghi, Elisabetta Bolli, Anna Maria Granato, Laura Ridolfi, Federica Gabrielli, Alessandra Barucca, Antonio Concetti, Ruggero Ridolfi, Angela Riccobon

Research output: Contribution to journalArticle

Abstract

Previous studies have shown that tumor endothelial markers (TEMs 1-9) are up modulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. We recently reported that monocyte-derived DCs used for vaccination trials may accumulate high levels of TEM8 gene transcripts. Here, we investigate whether TEM8 expression in DC preparations represents a specific tumor-associated change of potential clinical relevance. TEM8 expression at the mRNA and protein level was evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis in human clinical grade DCs utilized for the therapeutic vaccination of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma). The analyses revealed that DCs from patients markedly differ in their ability to up-modulate TEM8. Indeed, mDCs from eight non-progressing patients [median overall survival (OS) = 32 months, all positive to the delayed-type hypersensitivity test (DTH)], had similar TEM8 mRNA expression levels [mDCs vs. immature iDCs; mean fold increase (mfi) = 1.97] to those found in healthy donors (mfi = 2.7). Conversely, mDCs from nine progressing patients (OS <5 months, all but one with negative DTH) showed an increase in TEM8 mRNA levels (mfi = 12.88, p = 0.0018). The present observations suggest that TEM8 expression levels in DC-based therapeutic vaccines would allow the selection of a subgroup of patients who are most likely to benefit from therapeutic vaccination.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume59
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Clinical outcome
  • Dendritic cells
  • Immunotherapy
  • Tumor endothelial marker 8

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

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  • Cite this

    Venanzi, F. M., Petrini, M., Fiammenghi, L., Bolli, E., Granato, A. M., Ridolfi, L., Gabrielli, F., Barucca, A., Concetti, A., Ridolfi, R., & Riccobon, A. (2010). Tumor endothelial marker 8 expression levels in dendritic cell-based cancer vaccines are related to clinical outcome. Cancer Immunology, Immunotherapy, 59(1), 27-34. https://doi.org/10.1007/s00262-009-0717-4