title: Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer.
abstract: Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P=0.016). Angiogenesis was significantly higher in treatment group (P=0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P=0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.
authors.affiliation: Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: T T
authors.initials: TT
authors.lastname: Sahin
authors.forename: H
authors.initials: H
authors.lastname: Kasuya
authors.forename: N
authors.initials: N
authors.lastname: Nomura
authors.forename: T
authors.initials: T
authors.lastname: Shikano
authors.forename: K
authors.initials: K
authors.lastname: Yamamura
authors.forename: T
authors.initials: T
authors.lastname: Gewen
authors.forename: A
authors.initials: A
authors.lastname: Kanzaki
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Sugae
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: S
authors.initials: S
authors.lastname: Nomoto
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: H
authors.initials: H
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Kikumori
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: A
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D005260:Female; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000235:genetics* / Q000276:immunology