title: Predicting tumor outcome following cancer vaccination by monitoring quantitative and qualitative CD8+ T cell parameters.
abstract: Identification of reliable surrogate predictors for evaluation of cancer vaccine efficacy is a critical issue in immunotherapy. We analyzed quantitative and qualitative CD8+ T cell parameters in a large pool of BALB/c mice that were DNA-vaccinated against P1A self tumor-specific Ag. After immunization, mice were splenectomized and kept alive for a subsequent tumor challenge to correlate results of immune monitoring assays with tumor regression or progression in each individual animal, and to assess the prognostic value of the assays. The parameters tested were 1) percentage of in vivo vaccine-induced tumor-specific CD8+ T cells; 2) results of ELISPOT tests from fresh splenocytes; 3) percentage of tumor-specific CD8+ T cells in culture after in vitro restimulation; 4) in vitro increase of tumor-specific CD8+ T cell population expressed as fold of expansion; and 5) antitumor lytic activity of restimulated cultures. Except for the ELISPOT assay, each parameter tested was shown by univariate statistical analysis to correlate with tumor regression. However, multivariate analysis revealed that only in vitro percentage of Ag-specific CD8+ T cells was an independent prognostic factor that predicted tumor outcome. These findings should be considered in the design of new immune monitoring systems used in cancer immunotherapy studies.
authors.affiliation: Department of Oncology and Surgical Sciences, University of Padova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Alessia
authors.initials: A
authors.lastname: Zoso
authors.forename: Silvia
authors.initials: S
authors.lastname: Dalla Santa
authors.forename: Gabriella
authors.initials: G
authors.lastname: Milan
authors.forename: Paola
authors.initials: P
authors.lastname: Del Bianco
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: De Salvo
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic / Q000706:statistics & numerical data; D004797:Enzyme-Linked Immunosorbent Assay / Q000706:statistics & numerical data; D005260:Female; D018655:Lymphocyte Count / Q000706:statistics & numerical data; D051379:Mice; D008807:Mice, Inbred BALB C; D015166:Monitoring, Immunologic / Q000379:methods / Q000706:statistics & numerical data; D015999:Multivariate Analysis; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D019444:Vaccines, DNA; C507749:cancer-testis antigen P1A, mouse