TRAFFICKING OF ACTIVATED LYMPHOCYTES INTO THE RENCA TUMOR MICROCIRCULATION IN-VIVO IN MICE

The aim of the study was to establish a model of tumour microcirculati on in vivo using the murine renal cell carcinoma cell line (RENCA) imp lanted into the mouse cremaster muscle, and subsequently to investigat e the trafficking of syngeneic lymphocyte subpopulations into both the RENCA tumour and the surrounding normal cremaster muscle microcircula tion. We have demonstrated that RENCA tumour cells, at a dose of 1.5 x 10(5) per 30 mu l injected into the cremaster muscle, reproducibly pr oduced a vascularized tumour suitable for in vivo microscopy at 10-14 days. Injection of fluorescently labelled effector cells (1 x 10(6)) i ncluding naive splenocytes, T-cell enriched populations and ex vivo in terleukin 2 (IL-2)-activated splenocytes all migrated to and flowed th rough both the tumour and the normal microcirculation, with negligible adhesion. However, we observed the selective recruitment, localizatio n and arrest of IL-2-activated splenocytes (P < 0.05) into the tumour microcirculation, and the subsequent extravasation of cells into the t umour intestitium in some instances. This did not occur with the other effector cells. We also observed the absence of leucocyte rolling in the tumour microcirculation, suggesting an impairment in adhesion mole cule expression on the tumour endothelium. We have therefore establish ed the potential of this model for defining further effector cell-tumo ur-endothelium interactions.