title: The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses.
abstract: BACKGROUND
  Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH(+) with respect to DTH(-) unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood.
  
  
  METHODS
  Healthy donors and melanoma patient's lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release.
  
  
  CONCLUSIONS
  Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4(+) TGF-β(+)) regulatory T lymphocytes compared with healthy donors. Notably, DTH(+) patients showed a threefold reduction of Th3 cells compared with DTH(-) patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-γ releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH(+) with respect to DTH(-) patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response.
  
  
  CONCLUSIONS
  Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients.
authors.affiliation: Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, 8380453, Santiago, Chile. duran.aniotz@gmail.com
authors.forename: Claudia
authors.initials: C
authors.lastname: Durán-Aniotz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Segal
authors.forename: Lorena
authors.initials: L
authors.lastname: Salazar
authors.forename: Cristián
authors.initials: C
authors.lastname: Pereda
authors.forename: Cristián
authors.initials: C
authors.lastname: Falcón
authors.forename: Fabián
authors.initials: F
authors.lastname: Tempio
authors.forename: Raquel
authors.initials: R
authors.lastname: Aguilera
authors.forename: Rodrigo
authors.initials: R
authors.lastname: González
authors.forename: Claudio
authors.initials: C
authors.lastname: Pérez
authors.forename: Andrés
authors.initials: A
authors.lastname: Tittarelli
authors.forename: Diego
authors.initials: D
authors.lastname: Catalán
authors.forename: Bruno
authors.initials: B
authors.lastname: Nervi
authors.forename: Milton
authors.initials: M
authors.lastname: Larrondo
authors.forename: Flavio
authors.initials: F
authors.lastname: Salazar-Onfray
authors.forename: Mercedes N
authors.initials: MN
authors.lastname: López
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines