SUPPRESSION OF BURKITTS-LYMPHOMA TUMORIGENICITY IN NUDE-MICE BY CO-INOCULATION OF EBV-IMMORTALIZED LYMPHOBLASTOID-CELLS

EBV-immortalized B-lymphoblastoid cell lines (LCL) inoculated s.c. int o T-cell-deficient nude mice regress completely after a short initial growth period. We tested whether the putative host response underlying this phenomenon might also be directed against progressively growing Burkitt's lymphoma (BL) tumors in nude mice. Outgrowth of BL tumors wa s suppressed when cells of the highly tumorigenic BL cell line BL 60 w ere mixed with cells of the autologous LCL IARC 277 before s.c. inocul ation into nude mice. Even when the cells were inoculated separately a nd simultaneously into contralateral flanks of the mice, regression of initially growing BL tumors could be observed, albeit with reduced fr equency and dependent on the dose of LCL cells. Tumor growth of BL 60 cells could also be suppressed by co-inoculation with the non-autologo us LCL IARC 174 and IARC 277 cells could suppress growth of the non-au tologous BL cell line Eli. Pronounced infiltration with murine (m)CD-I Ib-positive mouse macrophages and mCD-8a-positive mouse lymphoid cells , most probably natural killer cells, was seen in histological tissue sections of regressing BL 60 tumors when LCL cells were inoculated con tralaterally. In regressing BL tumors, these mouse cells were present not only in necrotic areas but also in vital BL tissue, indicating tha t infiltration of mouse cells had taken place before the development o f necrosis. Since tumor-infiltrating mouse cells can be activated at l east by some human cytokines, we measured cytokine production of BL 60 and IARC 277. High amounts of IL 6 and IL 10 were produced by the LCL cells, whereas IL-6 and IL-10 production by the BL 60 cells was beyon d or close to the detection threshold. In addition, IL 8 was secreted up to 5-fold move by the LCL than by the BL cells. The results present ed here thus suggest a host response of the nude mouse, which is trigg ered by cytokines released from the LCL but, once induced, is directed also against BL cells. (C) 1995 Wiley-Liss, Inc.