title: Neoadjuvant anti-tumor vaccination prior to surgery enhances survival.
abstract: BACKGROUND
  This study was conducted to determine if anti-tumor vaccination administered prior to partial debulking surgery could improve survival using a murine solid tumour model.
  
  
  METHODS
  Tumor incidence and survival rates were compared in mice bearing subcutaneous AB1-HA mesothelioma tumors that received either sham surgery, debulking surgery or vaccination prior to debulking surgery. Additionally, mice were depleted of CD4 and/or CD8 T lymphocytes during vaccination to assess their involvement in vaccine induced anti-tumor immunity. Flow cytometry was performed to characterise changes in the proportion and activation status of immune cells associated with anti-tumor immunity.
  
  
  RESULTS
  Neoadjuvant vaccination combined with debulking surgery resulted in decreased tumor burden, increased survival and generation of tumor-specific immunity compared to surgery alone. Depletion of CD8 T cells completely abrogated any vaccine induced anti-tumor immune response. Conversely, CD4 depletion enhanced CD8 T cell activation resulting in complete tumor regression in 70% of mice treated with combined surgery and vaccination therapy. Tumor free survival was associated with established immunological memory as defined by the induction of effector memory T cells and resistance to rechallenge with parental AB1 mesothelioma cells.
  
  
  CONCLUSIONS
  Neoadjuvant anti-cancer vaccination combined with partial debulking surgery induced CD8-dependent anti-tumor immunity that significantly delayed tumor outgrowth relative to surgery alone. Complete tumor eradication was observed when vaccination and surgery were performed in CD4 T cell depleted animals. This demonstrates that adjuvant immunotherapy can improve post-surgical survival following cancer debulking surgery and provides a scientific rational for clinical trials of such an approach.
authors.affiliation: School of Medicine & Pharmacology, University of Western Australia, Perth, 4th Floor, G Block, Queen Elizabeth II Medical Centre, Perth 6009, WA, Australia. scott.fisher@uwa.edu.au.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Amanda
authors.initials: A
authors.lastname: Cleaver
authors.forename: Devina D
authors.initials: DD
authors.lastname: Lakhiani
authors.forename: Andrea
authors.initials: A
authors.lastname: Khong
authors.forename: Theresa
authors.initials: T
authors.lastname: Connor
authors.forename: Ben
authors.initials: B
authors.lastname: Wylie
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Lesterhuis
authors.forename: Bruce W S
authors.initials: BW
authors.lastname: Robinson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D020360:Neoadjuvant Therapy / Q000379:methods*; D009369:Neoplasms / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D047368:Tumor Burden; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines