Observations on the Increasing Malignancy of Tumours on Prolonged Growth: The Influence of Immunological Changes in the Host

Spontaneously occurring A-strain mouse mammary carcinomata were individually passaged, at equal intervals into separate groups of isogenic hosts. The tumours showed evidence of increasing autonomy as judged either by the decreasing host lymphoid hyperplasia they evoked, or their decreased killing time, as passaging continued. However, in general, no reduction was found in the ability of spleen cells from hosts bearing succeeding passages of the same tumour to induce a graft-versus-host reaction in (A × CBA)F1 hybrid mice. It is therefore suggested that the increasing malignancy of the tumours studied was associated with a change in the tumour rather than increasing immunodepression in successive hosts

Evidence of Loss of Tumour-specific Antigen on Repeatedly Transplanting a Tumour in the Strain of Origin

SPLENOMEGALY has often been observed in mice bearing tumour transplants, and can occur even when the tumour originated in an animal isogenic with the recipient. This may sometimes be due, as has been suggested, to associated infection, or to extra-medullary haemopoiesis resulting from tumour-induced anaemia (van Ebbenhorst Tengbergen and Muhlbock, 1958). In experiments reported previously from this laboratory, however, splenomegaly developed regularly in the absence of infection in A-strain mice which received transplants of a spontaneous A-strain mammary carcinoma, or of the same tumour after 1-5 passages each of 2-3 weeks ' duration, and as the histological findings were characteristic of immunological stimulation it was concluded that the tumour possessed one or more antigens which were not represented in normal A-strain tissues (Woodruff and Symes, 1962). Subsequently, a chance observation suggested that after many passages the tumour was no longer capable of eliciting splenomegaly in the A-strain, and the following experiments were designed to investigate the matter

Further Observations on Whether Host Immunodepression is Associated with Tumour Growth in Mice

In order to investigate whether the presence of a tumour was associated with immunodepression in the host, spleen cells from parent line animals with tumours were injected intravenously into F1 hybrids, half of which carried the same tumour. Further groups of F1 hybrid with and without the tumour received spleen cells from non-tumour bearing parent line animals. The G.V.H. reactions induced in the four groups of F1 hybrid were compared and no significant differences were found. This was true in separate experiments, involving two mammary carcinomata and a 3-methylcholanthrene induced sarcoma, wherein the period of tumour growth in the parent line donor and F1 hybrid recipient was varied

The Significance of Splenomegaly in Tumour-Bearing Mice

of the spleen and lvmph nodes occurred in (15713R mice which received transplants that enlargemelit of an A-strain tumour, Sarcoma 1, towhich thev were not susceptible. Thev attributed this to an immunological re,-,ction, but did not offer any explanation of the fact that splenic and 1Vmph node enlargement occurred also in susceptible (Astrain) mice which received transplants of the same tumour. The present investigation began with the observation that splenic enlargement occurred regularlv in A-strain female mice with spontaneous mammary cancer, and also in female A-strain Pnd (A x ASW)F1 hvbrid mice bearing transplants of ati A-strain mammarv carCinoma, but not;-C.9 a rule in mice of non-susceptible strains which received similar transplants. We h,,ive gone on to study the phenomenon in iiiore detail, aiid in particular to det-ermine firstlv-%A-hether splenomegalv can be produced in susceptible mice with cell-free tumour textracts, and secondly, whether it occurs when the tumour is transplai-ited to animals which are normall

The Effect of Rat Spleen Cells on Two Transplanted Mouse Tumours

IT was reported in a previous paper (Woodruff and Symes, 1962a) that the growth, in A-strain mice, of subcutaneous transplants of a mammary carcinoma which originated in this strain, could be greatly retarded, and the tumour could sometimes be completely destroyed, by giving a sublethal dose of whole body irradiation followed by an intravenous injection of allogeneic spleen cells from either a normal CBA mouse or a CBA mouse which had been immunized against the A-strain tumour. Due to the concomitant induction of graft-versus-host disease, however, these procedures sometimes resulted in early death of the treated animals while the growth of their tumours remained arrested. The present experiments are concerned with the effect of an intraperitoneal injection of heterogeneic spleen cells from normal or pre-immunized rats, preceded in some cases by sublethal whole body irradiation, on mice previously injected by the same route with the Landschutz ascites tumour or with a cell suspension prepared from an A-strain mammary carcinoma. Previous observations on the anti-tumour effect of heterogeneic cells have bee