The association of cytotoxic cytokines in DCV-treated patients suggests new helper cells sustained a persistent Th1-response, while in TCV-treated patients only a Th2-response persisted
The association of cytotoxic cytokines in DCV-treated patients suggests new helper cells sustained a persistent Th1-response, while in TCV-treated patients only a Th2-response persisted. 12967_2020_2328_MOESM11_ESM.docx (11K) GUID:?EE0E74C4-0EA1-4220-9168-0386D0D38AEB Additional file 12. First 2 canonical discriminant functions explain 100% of variance. 12967_2020_2328_MOESM12_ESM.docx (11K) GUID:?2563CADE-EFFE-4612-93D8-C52B6804B6A0 Additional file 13. First 2 canonical discriminant Vinorelbine (Navelbine) functions used in the analysis explain 100% of variance. 12967_2020_2328_MOESM13_ESM.docx (11K) GUID:?2B3AF35B-2AC7-4FBD-8F03-A476927137A6 Additional file 14. Wilks Lambda test of functions. 12967_2020_2328_MOESM14_ESM.docx (11K) GUID:?7751B94E-F5B5-4EEB-B439-FE7207C042C4 Additional file 15. Cox regression using IgM baseline values. 12967_2020_2328_MOESM15_ESM.docx (11K) GUID:?FD7D419B-03B4-4C4E-9C02-E27F35BBCB90 Data Vinorelbine (Navelbine) Availability StatementThe clinical and proteomic datasets analyzed during the current study are available from your corresponding author on affordable request. Abstract Background In a randomized phase II trial conducted in patients with metastatic melanoma, patient-specific autologous dendritic cell vaccines (DCV) were associated with longer survival than autologous tumor cell vaccines (TCV). Both vaccines offered antigens from cell-renewing autologous tumor cells. The current analysis was performed to better understand the immune responses induced by these vaccines, and their association with survival. Methods 110 proteomic markers were measured at a week-0 baseline, 1?week before the first of 3 weekly vaccine injections, and at week-4, 1?week after the third injection. Data was offered as a deviation from normal controls. A Vinorelbine (Navelbine) two-component principal component (PC) statistical analysis and discriminant analysis were performed on this data set for all those patients and for each treatment cohort. Results At baseline PC-1 contained 64.4% of the variance and included the majority of cytokines associated with Th1 and Th2 responses, which positively correlated with beta-2-microglobulin (B2M), programmed death protein-1 (PD-1) and transforming growth factor beta (TGF1). Results were comparable at baseline for both treatment cohorts. After three injections, DCV-treated DCN patients showed correlative grouping among Th1/Th17 cytokines on PC-1, with an inverse correlation with B2M, FAS, and IL-18, and Vinorelbine (Navelbine) correlations among immunoglobulins in PC-2. TCV-treated patients showed a positive correlation on PC-1 among most of the cytokines and tumor markers B2M and FAS receptor. There were also correlative changes of IL12p40 with both Th1 and Th2 cytokines and TGF1. Vinorelbine (Navelbine) Discriminant analysis provided additional evidence that DCV was associated with innate, Th1/Th17, and Th2 responses while TCV was only associated with innate and Th2 responses. Conclusions These analyses confirm that DCV induced a different immune response than that induced by TCV, and these immune responses were associated with improved survival. Clinical trials.gov NCT004936930 retrospectively registered 28 July 2009 Keywords: Proteomics, Principal component analysis, Discriminant analysis, Metastatic melanoma, Dendritic cells, Malignancy vaccines Background The development of effective therapeutic malignancy vaccines has been an elusive goal for several decades. The Nobel Prize winning research of Ralph Steinman [1, 2] has led to a resurgence of interest in therapeutic dendritic cell vaccines (DCV) [3, 4], especially in patients with metastatic melanoma [5]. Clinical studies utilizing autologous dendritic cells loaded with antigens from autologous tumor cells have been especially encouraging [6C9]. A randomized phase II trial tested two vaccines featuring autologous tumor antigens (ATA): injections of autologous dendritic cells loaded ex lover vivo with antigens from autologous tumor cell lines (DCV), and tumor cell vaccines (TCV) consisting of irradiated autologous proliferating tumor cells [8, 9]. An early analysis showed that DCV was associated with better survival [8], and this was confirmed when 5-12 months follow up showed a more than doubling of median survival and 3-12 months survival rate, and a 70% reduction in the risk of death [9]. This DCV approach is currently being tested in phase II trials in glioblastoma and ovarian malignancy, and in a phase IB trial in combination with monoclonal antibodies to programmed death-1 protein (PD-1) in melanoma patients. The human immune response to pathogens and malignancy has many interacting components encompassed by concepts of innate and adaptive immunity [10, 11]. Inducing new immune responses, or enhancing existing weak immune responses to malignancy associated antigens, is the goal of anti-cancer vaccines.