Quantitative studies on the transplantability of murine and human tumors into the brain and subcutaneous tissues of NCr/Sed nude mice.

The transplantability of experimental tumors into the brain (i.c.) and s.c. tissues of C3Hf/Sed and athymic NCr/Sed nude mice was examined using quantitative cell transplantation assays. Studies using the immune-competent C3H animals showed that brain is a more favorable site for the transplantation of syngeneic tumor than s.c. tissue and that this is true for nonimmunogenic as well as immunogenic tumors. The capacity of the brain to act as an immunological sanctuary can be overwhelmed by a strong, systemic, secondary immune response such as that evoked by the methylcholanthrene-induced sarcoma FSal. In studies performed using NCr/Sed nude mice, the allogeneic tumor MCaIV was found not to be demonstrably immunogenic. The cell dose required to transplant the tumor into 50% of recipients (TD50) could neither be increased by immunization procedures nor decreased by six Gy whole-body irradiation (WBI) prior to transplantation. Delayed-type hypersensitivity to this tumor was not expressed by nude mice after rechallenge with tumor antigen. The TD50 was again lower for i.c. than s.c. transplantation and the ratio s.c./i.c. was comparable to that found in syngeneic C3Hf/Sed hosts. Three human tumors have been similarly tested. They were: FaDu, a pharyngeal squamous carcinoma; HFSal, a fibrosarcoma; and U87, a malignant glioma. s.c. TD50 values were in all cases significantly higher than those obtained i.c. The ratios TD50 s.c./i.c. ranged from 6.4 to greater than 50 in five studies, substantially higher than those found for transplantation of murine tumors into either the syngeneic or the allogeneic recipients. Six Gy WBI reduced the s.c. TD50 for these tumors, but in each case the value remained significantly higher than that obtained i.c. 19.4 Gy WBI given in 10 equal fractions and followed by i.v. bone marrow rescue reduced further the s.c. TD50 for FaDu. NCr/Sed nude mice demonstrated cross-reacting delayed-type hypersensitivity against FaDu and HFSal. A small proportion of FaDu tumors (less than 2%) displayed a spontaneous halt in growth or even regression. When the host cell infiltrate of these tumors was analyzed, an increase was seen in the proportion of Thy 1.2 and asialo-GM1-positive cells as compared with progressively growing tumors. These data strongly suggest that a residual low level of immune reactivity exists in nude mice against xenotransplanted human tumors. This resistance to s.c. transplantation may be diminished by WBI and is less for intracerebral implantation.