title: Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate.
abstract: Patients with metastatic renal cell carcinoma (mRCC) have a limited life expectancy but still a subset of these patients develop immune and clinical responses after immunotherapy including dendritic cell (DC) vaccination. In a recently published phase I/II trials, fourteen HLA-A2 negative patients with progressive mRCC were vaccinated with autologous DC pulsed with allogeneic tumour lysate. Low-dose IL-2 administered subcutaneously was given concomitantly. In this study, we analysed lysate specific proliferation of PBMCs from these patients together with the TH1/TH2 balance of the responding T cells. Also, serum concentrations of IL-10, IL-12, IL-15, IL-17 and IL-18 from these patients and additional thirteen HLA-A2 positive mRCC patients treated with autologous DC pulsed with survivin and telomerase peptides were analysed during vaccination to identify systemic immune responses and potential response biomarkers. In HLA-A2 negative mRCC patients a spontaneous predominance of TH1 secreting tumour lysate specific T cells was observed prior to vaccination in patients attaining stable disease (SD) during treatment whereas patients with continued progressive disease (PD) had a mixed TH1/TH2 response. The TH1/TH2 balance was unchanged during vaccination also when tumour lysate specific T cell responses increased. An increase in IL-12, IL-17 and IL-18 serum concentrations was observed during vaccination but no difference between patients with SD and PD was observed. IL-10 or IL-15 was not measurable in serum.
authors.affiliation: Department of International Health, Immunology and Microbiology, The Panum Institute, University of Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Soleimani
authors.forename: A
authors.initials: A
authors.lastname: Berntsen
authors.forename: I M
authors.initials: IM
authors.lastname: Svane
authors.forename: A E
authors.initials: AE
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D015789:HLA-A2 Antigen