THE PHENOTYPIC CHANGES IN TUMOR-INFILTRATING LYMPHOCYTES AND TUMOR-CELLS FOLLOWING INTRAARTERIAL INFUSION OF INTERLEUKIN-2 IN PATIENTS WITHSQUAMOUS-CELL CARCINOMA

This study evaluates the morphological and phenotypic changes that occ ur in squamous cell carcinoma of the head and neck when local infusion s 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 IO days. Biopsies of th e tumour were taken pre- and 48h post-therapy, snap-frozen, cut, and e xamined histologically and immunocytochemically. Local infusions of IL -2 increase the numbers of antigen-presenting Langerhans cells (CD1a-p ositive) and infiltrating lymphoqtes, 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 su rface of the tumour cells, capillary and post-capillary endothelial ce lls, 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 int ra-arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cyto kines, since in vivo they are mainly produced and act locally. Further more, 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.