Tumor endothelial marker 8 expression levels in dendritic cell-based cancer vaccines are related to clinical outcome.
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.
Unit of Translational Biology, Department of Biology M.C.A., University of Camerino, via Gentile da Varano III, Camerino (MC), Italy. franco.venanzi@unicam.it
Franco Maria
FM
Venanzi
Massimiliano
M
Petrini
Laura
L
Fiammenghi
Elisabetta
E
Bolli
Anna Maria
AM
Granato
Laura
L
Ridolfi
Federica
F
Gabrielli
Alessandra
A
Barucca
Antonio
A
Concetti
Ruggero
R
Ridolfi
Angela
A
Riccobon
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000276:immunology; D014611:Vaccination
C473287:ANTXR1 protein, human; D019496:Cancer Vaccines; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface