Scientific Literature

Immune cell profiling of melanoma metastases from patients treated with TriMixDC-MEL dendritic cell therapy in combination with ipilimumab.

K. Schats, E. A. Van Vre, I. Debyser, A. Vandenbroeck, Y. Jansen, T. Seremet, K. Marien, E. Fransen, D. Schrijvers, W. Van Criekinge, K. Thielemans, B. Neyns, I. De Meester, M. Kockx , Journal of Clinical Oncology , DOI: 10.1200/JCO.2017.35.15_suppl.e21030

Background: Ipilimumab has proven clinical benefit in a subset of melanoma patients. Previously a high rate of durable complete response was shown with the combination of ipilumumab and TriMixDC-MEL therapy (Wilgenhof et al. JCO 2016).
Melanoma metastases were collected from patients, before initiation of combined ipilimumab and dendritic cell (TrimixDC-MEL) therapy [NCT01302496]. Formalin-fixed, paraffin-embedded samples were available from 24 patients of which 6 had durable benefit (DB) and 18 had no clinical benefit (NB). Serial 4µm slides were stained with immunohistochemistry (IHC) for immune response markers. Semi-automated analysis (Definiens software) was applied to estimate the tumor area stained for CD8, CD20, CD163, OX40, ICOS and LAG3, % of FOXP3 positive T-cells and IRF1-positive tumor nuclei. H-scores were calculated for IDO, STING and MHC-I on tumor cells (TC). A qualified pathologist scored the % PD-L1 on TC and immune cells (IC). In addition, RNA was extracted (n = 19) and analyzed using the NanoString nCounter Pan Cancer immune profiling panel.

The IHC and NanoString variables were tested for predictive response, as single marker using logistic regression and the area under the curve
(AUC) values. The top 15 biomarkers for either IHC or NanoString are listed in the table below (AUC in descending order). Gene Ontology analysis (GOstat) of Nanostring markers revealed over-representation of genes involved in the response to other organisms (GO: 0051707) and viruses (GO: 0009615) in DB patients.
This study identified a set of potentially new predictive biomarkers, including virus response related genes, for DB following ipilimumab plus TriMixDC-MEL therapy. Further prospective validation is warranted.