AN IN-VIVO MODEL TO COMPARE HUMAN-LEUKOCYTE INFILTRATION IN CARCINOMAXENOGRAFTS PRODUCING DIFFERENT CHEMOKINES

In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carc inoma, were analyzed by reverse transcriptase-polymerase chain reactio n (RT-PCR), immunofluorescence and ELISA for the expression and in vit ro production of cytokines with chemotactic, proinflammatory and growt h-stimulating activity. Although both cell lines displayed a constitut ive expression of granulocyte colony-stimulating factor (G-CSF), granu locyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and I L-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Act ivation, Normal T Expressed and Secreted) and monocyte-activating prot ein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on s ections from tumors xenografted in nude mice. To analyze whether the t umor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral brood leukocytes injected in the proximity of SK-OY-3 and of CALU-3 tumor xenografts. While SK- OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45(+) cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr. (C) 1995 Wiley-Liss, Inc.