Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination.
INTRODUCTION. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. MATERIAL AND METHODS. Plasma and serum samples were collected prior to vaccination and continuously during treatment. GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 instrument. CEA and TIMP-1 were analysed on ELISA platforms. RESULTS. Patients achieving stable disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. CONCLUSION. The increased levels of key pro-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine.
Department of Surgical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark. stefan@stefanburgdorf.dk
Stefan K
SK
Burgdorf
Mogens H
MH
Claesson
Hans J
HJ
Nielsen
Jacob
J
Rosenberg
D014408:Biomarkers, Tumor / Q000097:blood; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation; D018417:Th1 Cells / Q000276:immunology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D019715:Tissue Inhibitor of Metalloproteinase-1