ADHESION MOLECULE EXPRESSION AND LEUKOCYTE TRAFFICKING FOLLOWING IMMUNOTHERAPY WITH RECOMBINANT INTERLEUKIN-2

The relevant anti-tumour mechanisms of recombinant interleukin-2 (rIL- 2) in vivo are unclear but an influx of T-lymphocytes and macrophages has been noted in regressing lesions. One of the dose limiting toxicit ies of rIL-2 is the development of a capillary leak syndrome attribute d to widespread endothelial activation. Changes in expression of endot helial and leucocyte-associated adhesion molecules were assessed in tu mour and uninvolved skin in patients with metastatic breast cancer rec eiving rIL-2. Increased expression of intracellular adhesion molecule- 1, its leucocyte-associated ligand, leucocyte function associated mole cule-1, vascular cell adhesion molecule and its ligand, very late afte r activation antigen-4 as well as members of the selectin family of ad hesion molecules, were noted in uninvolved skin following rIL-2. Expre ssion of these adhesion molecules was noted in tumour stroma before rI L-2 but little change was observed following rIL-2 infusion. An influx of monocytes and T-lymphocytes (expressing the IL-2 receptor and of t he memory subtype) and a lower number of neutrophils was noted in unin volved skin following rIL-2, Although monocytes and T-lymphocytes were present in tumour stroma before rIL-2 no changes were observed follow ing infusion. The changes noted in the dermis contrast with those seen at tumour sites and may partly explain the low therapeutic index of r IL-2.