Immunobiological aspects of the nude mouse model relative to human cancer chemosensitivity tests.

The nude mouse model (NMM) has been proposed for testing chemosensitivity of human cancer cells with encouraging results. However, nude mice cannot be considered as unreactive "test tube" recipients of allogeneic or xenogeneic tissues, since a variety of immunological functions are fully represented in these hosts. In general, graft resistance against tumour cells can be classified as: (a) elicitable responses (ER), thymus-dependent, evoked by tumour-associated antigens; (b) natural resistance (NR), T-independent, not requiring previous exposure to transplantation antigens. Graft resistance may therefore play a substantial role even in the absence of a functional T-cell system. This has been demonstrated in irradiated euthymic mice capable of rejecting Hh-incompatible lymphomas, and in nude mice, where NR-type responses are particularly efficient, either in vitro or in vivo. It is reasonable to assume that these responses could interfere with tumour responsiveness to the chemotherapeutic effects of drugs. In fact, marked synergistic effects have been observed in conventional hosts combining chemotherapy with limited ER, or with Hh-type NR present in lethally irradiated mice. Similar combined effects could occur in nude mice bearing NR-susceptible human tumours in the course of chemosensitivity assays. These considerations have led to the search for privileged sites associated with low levels of NR; previous results show that these responses appear to be substantially absent in the brains of conventional mice and extremely low in the same organ of congenitally athymic hosts. It follows that the brain of the nude mouse appears to be a suitable site for human tumour cell growth, unaffected by or minimally subjected to NR.