EXPRESSION OF ICAM-1 ENHANCES IN-VIVO LYMPHOCYTE ADHESION IN A MURINEFIBROSARCOMA

Background and Objectives: ICAM-1 is essential for lymphocyte-endothel ial cell interactions. We have demonstrated that increased expression of ICAM-1 in tumors results in an enhanced response to adoptive immuno therapy. We undertook this study to determine whether increased expres sion of ICAM-1 results in increased lymphocyte adhesion in vivo. Metho ds: Parental MCA-105 tumor cells were cotransfected with ICAM-1 and th e NeoR plasmid. A neomycin resistant clone (C1149) was selected and in creased expression of ICAM-1 confirmed by FAGS analysis. Tumor fragmen ts (MCA-105 or C1149) were placed in a dorsal skinfold chamber on day 0 in C57BL/6 mice. Lymphocytes were fluorescently labeled using 0.5% a cridine orange and activity recorded on videotape at 700x magnificatio n. Lymphocyte activity was quantitated over 30 second intervals in pos tcapillary venules as either passing or rolling/sticking (R/S). The % R/S was calculated for each category and evaluated using chi(2) analys is. Results: Whereas 38% of lymphocytes were classified as R/S in norm al tissue, 32% were classified as R/S (P >.05) in the MCA-105 tumor. H owever, in the ICAM-1 transfected CL149, there was significantly great er R/S at 53% (P <.05). Conclusions: These data demonstrate increased lymphocyte adhesion in tumors with enhanced expression of ICAM-1 by di rect in vivo observations and may partially explain the salutary effec t of increased ICAM-1 expression on adoptive immunotherapy. This sugge sts the possible application of adhesion molecule expression in the ce llular therapy of cancer. (C) 1997 Wiley-Liss, Inc.