title: The phenotypic changes in tumour infiltrating lymphocytes and tumour cells following intra-arterial infusion of interleukin-2 in patients with squamous cell carcinoma.
abstract: This study evaluates the morphological and phenotypic changes that occur in squamous cell carcinoma of the head and neck when local infusions of interleukin-2 (IL-2) are given. Twelve patients were treated with a range of doses of IL-2 (3 x 10(3) to 3 x 10(6) international units/day) by continuous intra-arterial infusion for 10 days. Biopsies of the tumour were taken pre- and 48 h post-therapy, snap-frozen, cut, and examined histologically and immunocytochemically. Local infusions of IL-2 increase the numbers of antigen-presenting Langerhans cells (CD1a-positive) and infiltrating lymphocytes, predominantly of the CD3 and CD4 (T-helper) phenotypes. Locally infused IL-2 results in the expression of MHC (major histocompatibility complex) class II antigens on the surface of the tumour cells, capillary and post-capillary endothelial cells, and peri-tumoural macrophages. Intratumoural NK (natural killer) cells and CD8-positive (T-cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25 (IL-2 receptor) was only increased in those patients treated at the lower dose levels. The system of intra-arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cytokines, since in vivo they are mainly produced and act locally. Furthermore, the infused tumours are easily accessible to biopsy. The results from studies such as this may influence the design of tumour-targeted cytokine gene therapy programmes.
authors.affiliation: Department of Medicine, Royal Marsden Hospital, London, U.K.
authors.forename: J
authors.initials: J
authors.lastname: Salter
authors.forename: K A
authors.initials: KA
authors.lastname: Maclennan
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: G
authors.initials: G
authors.lastname: Dadian
authors.forename: P G
authors.initials: PG
authors.lastname: Riches
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007376:Interleukin-2 / Q000008:administration & dosage*; D007801:Langerhans Cells / Q000276:immunology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2