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

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.

• Authors: Franco Maria Venanzi, Massimiliano Petrini, Laura Fiammenghi, Elisabetta Bolli, Anna Maria Granato, Laura Ridolfi, Federica Gabrielli, Alessandra Barucca, Antonio Concetti, Ruggero Ridolfi, Angela Riccobon
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 59 Issue 1 Pg. 27-34 (Jan 2010) ISSN: 1432-0851 [Electronic] Germany
• PMID: 19440709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANTXR1 protein, human
• Cancer Vaccines
• Microfilament Proteins
• Neoplasm Proteins
• Receptors, Cell Surface

Topics

• Adult
• Aged
• Cancer Vaccines (immunology, metabolism, therapeutic use)
• Carcinoma, Renal Cell (immunology, therapy)
• Dendritic Cells (immunology, metabolism)
• Female
• Humans
• Male
• Melanoma (immunology, therapy)
• Microfilament Proteins
• Middle Aged
• Neoplasm Proteins (biosynthesis, immunology)
• Receptors, Cell Surface (biosynthesis, immunology)
• Vaccination