title: Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy.
abstract: Patients with glioblastoma multiforme (GBM) are profoundly immunosuppressed and may benefit from restoration of an antitumor immune response in combination with conventional radiation therapy and temozolomide (TMZ). The optimal strategies to evaluate clinically relevant immune responses to treatment have yet to be determined. The primary objective of our study was to determine immunologic response to cervical intranodal vaccination with autologous tumor lysate-loaded dendritic cells (DCs) in patients with GBM after radiation therapy and TMZ. We used a novel hierarchical clustering analysis of immune parameters measured before and after vaccination. Secondary objectives were to assess treatment feasibility and to correlate immune response with progression-free survival (PFS) and overall survival. Ten eligible patients received vaccination. Tumor-specific cytotoxic T-cell response measured after vaccination was enhanced for the precursor frequency of CD4+ T and CD4+ interferon γ-producing cells. Hierarchical clustering analysis of multiple functional outcomes discerned 2 groups of patients according to their immune response, and additionally showed that patients in the top quintile for at least one immune function parameter had improved survival. There were no serious adverse events related to DC vaccination. All patients were alive at 6 months after diagnosis and the 6-month PFS was 90%. The median PFS was 9.5 months and overall survival was 28 months. In patients with GBM, immune therapy with DC vaccination after radiation and TMZ resulted in tumor-specific immune responses that were associated with prolonged survival. Our data suggest that DC vaccination in combination with radiation and chemotherapy in patients with GBM is feasible, safe, and may induce tumor-specific immune responses.
authors.affiliation: Section of Hematology/Oncology-Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. Camilo.E.Fadul@hitchcock.org
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hampton
authors.forename: Enrico C
authors.initials: EC
authors.lastname: Lallana
authors.forename: Zhongze
authors.initials: Z
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Gui
authors.forename: Zbigniew M
authors.initials: ZM
authors.lastname: Szczepiorkowski
authors.forename: Tor D
authors.initials: TD
authors.lastname: Tosteson
authors.forename: C Harker
authors.initials: CH
authors.lastname: Rhodes
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wishart
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005909:Glioblastoma / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy; D012107:Research Design; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D000077204:Temozolomide; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D000939:Epitopes; D003606:Dacarbazine; D000077204:Temozolomide