Adhesion molecule expression and leucocyte 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 toxicities of rIL-2 is the development of a capillary leak syndrome attributed to widespread endothelial activation. Changes in expression of endothelial and leucocyte-associated adhesion molecules were assessed in tumour and uninvolved skin in patients with metastatic breast cancer receiving rIL-2. Increased expression of intracellular adhesion molecule-1, its leucocyte-associated ligand, leucocyte function associated molecule-1, vascular cell adhesion molecule and its ligand, very late after activation antigen-4 as well as members of the selectin family of adhesion molecules, were noted in uninvolved skin following rIL-2. Expression of these adhesion molecules was noted in tumour stroma before rIL-2 but little change was observed following rIL-2 infusion. An influx of monocytes and T-lymphocytes (expressing the IL-2 receptor and of the memory subtype) and a lower number of neutrophils was noted in uninvolved skin following rIL-2. Although monocytes and T-lymphocytes were present in tumour stroma before rIL-2 no changes were observed following infusion. The changes noted in the dermis contrast with those seen at tumour sites and may partly explain the low therapeutic index of rIL-2.
Miles
D W
DW
ICRF Clinical Oncology Unit, Guy's Hospital, London, UK.
Happerfield
L C
LC
Bobrow
L G
LG
Rubens
R D
RD
D000368:Aged; D001943:Breast Neoplasms / Q000628:therapy; D002277:Carcinoma / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000627:therapeutic use*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use
D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1