TY - JOUR
T1 - Tumor endothelial marker 8 expression levels in dendritic cell-based cancer vaccines are related to clinical outcome
AU - Venanzi, Franco Maria
AU - Petrini, Massimiliano
AU - Fiammenghi, Laura
AU - Bolli, Elisabetta
AU - Granato, Anna Maria
AU - Ridolfi, Laura
AU - Gabrielli, Federica
AU - Barucca, Alessandra
AU - Concetti, Antonio
AU - Ridolfi, Ruggero
AU - Riccobon, Angela
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Clinical outcome
KW - Dendritic cells
KW - Immunotherapy
KW - Tumor endothelial marker 8
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UR - http://www.scopus.com/inward/citedby.url?scp=70350101292&partnerID=8YFLogxK
U2 - 10.1007/s00262-009-0717-4
DO - 10.1007/s00262-009-0717-4
M3 - Article
C2 - 19440709
AN - SCOPUS:70350101292
SN - 0340-7004
VL - 59
SP - 27
EP - 34
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
IS - 1
ER -