A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin

Abstract

Extensive experience with isotransplants of 27 different tumours (leukaemias, sarcomata, carcinomata), all of strictly spontaneous origin in laboratory bred mice of low cancer strains CBA/Ht and WHT/Ht, has revealed no evidence of tumour immunogenicity. Of approximately 20,000 maintenance transplants, none failed and none regressed; of almost 10,000 carefully observed tumours arising from small or minimal inocula of tumour cells, none spontaneously regressed. The number of injected viable tumour cells required to give a 50% probability of successful transplantation (the TD50) ranged from approximately 1 cell to greater than 10,000 cells among the 27 tumours; high TD50 values, which were dramatically reduced by various procedures having no immunological significance, did not signify active "resistance" of the hosts. In the case of all of 7 randomly selected tumours, prior "immunization" of recipients with homologous lethally irradiated cells increased their tumour receptivity. Several experiments using various tumours failed to give evidence that immunity could be non-specifically induced or that a massive preponderance of lymphocytes from specifically sensitized mice could inhibit tumour transplantation or growth in vivo; no trace of "resistance" to tumour was adopted by isogeneic recipients of lymphocytes from regional nodes of tumour bearers. A limited review of the recent literature on tumour immunity shows that practically all the animal data presented in support of a general theory of tumour immunogenicity or to provide a basis for active clinical immunotherapy have been obtained from transplanted tumour systems which entail artefactual immunity associated with viral or chemical induction of the tumours or their allogeneic transplantation. It is suggested that isotransplants of spontaneously arising tumours are the only appropriate models of human cancer and that any genuine rapport between the animal laboratory and the clinic requires their exclusive use.

Further studies of the relationship between lymphatic dissemination and lymphnodal metastasis in non-immunogenic murine tumours

“…Evidence of the non-immunogenicity of these tumours appears elsewhere (Peters, 1975;Hewitt, Blake and Walder, 1976). CBA Carcinoma NT has featured in several previous experimental studies Hewitt, Blake and Porter, 1973;Peters and Hewitt, 1974).…”

Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy

“…Perhaps these drugs lessened a prostaglandin-induced inhibition of the immune system (Plescia et al, 1975). Although the NC carcinoma is thought to have low immunogenicity (Hewitt et al, 1976) FLU tended to increase the lymphocyte content of tumours . With regard to tumour spread, aspirin is antimetastatic in mice, possibly due to inhibition of platelet aggregation (Gasic et al, 1973).…”

“…The NC tumour used is a transplantable adenocarcinoma which originally arose spontaneously in the mammary gland of a WHT/ Ht mouse; it has been passaged subsequently in this inbred strain, and appears to be of low immunogenicity (Hewitt et al, 1976). The mice were injected with 106 NC carcinoma cells into the left flank, as described previously and the tumours wN-ere excised 2-3 weeks later under anaesthesia with ether or, in some experiments, pentobarbitone.…”

Facilitation of nodal metastasis from a non-immunogenic murine carcinoma by previous whole-body irradiation of tumour recipients

“…The experiments used material from the serial passage range 115 to 153, over which no changes in the characteristics of the tumour were observed. Previous studies had shown that no resistance against viable tumour cells could be induced by pretreatment of recipient mice with multiple doses of lethally irradiated homologous tumour cells (Hewitt, Blake and Walder, 1976).…”