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Expression of ICAM-1 enhances in vivo lymphocyte adhesion in a murine fibrosarcoma
J Turner1, J G Rhee, D F Fabian
1Department of Surgery, University of Maryland School of Medicine, Baltimore, USA.
Background And Objectives:
ICAM-1 is essential for lymphocyte-endothelial cell interactions. We have demonstrated that increased expression of ICAM-1 in tumors results in an enhanced response to adoptive immunotherapy. We undertook this study to determine whether increased expression of ICAM-1 results in increased lymphocyte adhesion in vivo.
Methods:
Parental MCA-105 tumor cells were cotransfected with ICAM-1 and the NeoR plasmid. A neomycin resistant clone (Cl149) was selected and increased expression of ICAM-1 confirmed by FACS analysis. Tumor fragments (MCA-105 or Cl149) were placed in a dorsal skin-fold chamber on day 0 in C57BL/6 mice. Lymphocytes were fluorescently labeled using 0.5% acridine orange and activity recorded on videotape at 700x magnification. Lymphocyte activity was quantitated over 30 second intervals in postcapillary venules as either passing or rolling/sticking (R/S). The % R/S was calculated for each category and evaluated using chi 2 analysis.
Results:
Whereas 38% of lymphocytes were classified as R/S in normal tissue, 32% were classified as R/S (P > .05) in the MCA-105 tumor. However, in the ICAM-1 transfected CL149, there was significantly greater R/S at 53% (P < .05).
Conclusions:
These data demonstrate increased lymphocyte adhesion in tumors with enhanced expression of ICAM-1 by direct in vivo observations and may partially explain the salutary effect of increased ICAM-1 expression on adoptive immunotherapy. This suggests the possible application of adhesion molecule expression in the cellular therapy of cancer.