Dendritic-Cell (DC)-Based Immunotherapy: Tumor Endothelial Marker 8 (TEM8) Gene Expression of DC Vaccines Correlates with Clinical Outcome

ABSTRACT Previous studies have shown that tumor-endothelial markers (TEMs) are upregulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. We reported that pro-angiogenic monocyte-derived DCs (Mo-DCs), utilized for therapeutic vaccination of cancer patients upon maturation, markedly differ in their ability to up-regulate tumor-endothelial marker 8 (TEM8) gene expression. A DC vaccination trial of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma), carried out at the Cancer Institute of Romagna (I.R.S.T.) in Meldola, highlighted a significant correlation between delayed-type hypersensitivity test (DTH) and overall survival (OS). In the study, relative TEM8 mRNA and protein expression levels (mature (m) vs. immature (i) DCs), in DCs obtained for therapeutic vaccines were evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis, respectively. mDCs from six healthy donors were included for comparison purposes. Eight non-progressing patients, all DTH-positive, had a mean fold increase (mfi) of 1.97 in TEM8 expression. Similarly, a TEM8 mRNA mfi = 2.7 was found in healthy donor mDCs. Conversely, mDCs from nine progressing patients, all but one with negative DTH, had a TEM8 mRNA mfi of 12.88. Thus, mDC TEM8 expression levels would seem to identify (p = 0.0018) patients who could benefit from DC therapeutic vaccination.