Studies with a spontaneous murine tumour--II. Transformation of non-inhibitory lymph node cells (LNC) of tumour bearers into tumour inhibitor cells in vitro.

Syngeneic BALB/c mice repeatedly pre-exposed to mitomycin-c-treated cells of a 'spontaneous' tumour SP/N-1 failed to develop resistance against the same tumour when tested by cell transfer assays. No difference could be observed between tumour-bearer, tumour-pretreated or normal donor LNC, or spleen cells by this assay system. When tumour-bearer LNC were cultured in vitro for 45 hr in the absence of tumour cells, these LNC generated a relatively strong ability to suppress tumour outgrowth in vivo following cell transfers. The tumour suppression appears to be due to tumour cell destruction since observation over four months or more in some experiments failed to reveal the presence of tumours at the site of inoculation. These findings clearly demonstrate that naturally arising tumours so often considered as devoid of, or weak in, tumour-associated transplantation antigens (TATA) may not necessarily be so. Despite the fact that the syngeneic host may be capable of recognizing TATA as foreign, the immune response initiated may not progress to completion in at least a proportion of these tumour-host systems. The defect appears to reside in the failure of differentiation of the pre-effector cells into the mature effector form. We interpret this as being due to a strong activation of certain inhibitors of essential lymphokine mediators such as interleukin 2, needed for differentiation and expansion of effector cell clones. It remains to be seen whether the mechanism of non-responsiveness or weakness of the response against many other members of this category of tumours--the 'spontaneous' or natural tumours--can be explained on the same basis as that of the SP/N-1 system studied here.