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

• Published in: Cancer Immunology, Immunotherapy Vol. 59; no. 1; pp. 27 - 34
• Main Authors: Venanzi, Franco Maria, Petrini, Massimiliano, Fiammenghi, Laura, Bolli, Elisabetta, Granato, Anna Maria, Ridolfi, Laura, Gabrielli, Federica, Barucca, Alessandra, Concetti, Antonio, Ridolfi, Ruggero, Riccobon, Angela
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-01-2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Cancer Research; Cancer Vaccines - immunology; Cancer Vaccines - metabolism; Cancer Vaccines - therapeutic use; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - therapy; Clinical outcomes; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Humans; Immunology; Immunotherapy; Male; Medical sciences; Medicine; Medicine & Public Health; Melanoma - immunology; Melanoma - therapy; Microfilament Proteins; Middle Aged; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - immunology; Oncology; Original; Original Article; Pharmacology. Drug treatments; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - immunology; Vaccination; Tumor endothelial marker 8; Clinical outcome; Dendritic cells; Immunotherapy; Dendritic cell; TEM8 gene; Prognosis; Treatment; Antigen presenting cell; Vaccine; Gene expression; Tumor cell
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-009-0717-4

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.