Is an immune reaction required for malignant transformation and cancer growth?

Increasing evidence has shown that probably all malignant mouse cells, even those of spontaneous sporadic cancers, are endowed with tumor-specific antigens. Stimulation of cancer growth, rather than inhibition by the immune reaction, is seemingly the prevalent effect in the animal of origin (the autochthonous animal). Small initial dosages of even strong tumor antigens tend to produce stimulatory immune reactions rather than tumor inhibition in any animal. Thus, an immune response at a low level may be an essential growth-driving feature of nascent cancers, and this may be why all cancers apparently have tumor-specific antigens. Inasmuch as a low level of immunity is stimulatory to tumor growth while larger dosages are inhibitory, immuno-selection via this low response may tend to keep the antitumor immune reaction weak and at a nearly maximal stimulatory level throughout most of a tumor’s existence. These facts suggest that both suppression of tumor immunity and a heightened immune reaction might each be therapeutic although very contrasting modalities

A new kink in an old theory of carcinogenesis

According to Berenblum’s two-stage hypothesis, the first stage in carcinogenesis is the production of benign premalignant lesions. Between this initiation stage and the formation of a malignant tumor there is often a long lag phase. We propose that this lag is caused by the delay in the formation of a new and rare tumor-specific antigen, which induces an immune response that stimulates tumor growth. Such tumor-specific antigens could arise as a result of a mutator-like phenotype, which is supposedly present in the benign initial stage of carcinogenesis. According to this hypothesis, the first stage lesion provides a weakly mutagenic environment conducive to the formation of the new antigen(s). If no such new antigens appear so there is no consequent immune response, it is argued that carcinogenesis would seldom if ever ensue

Cancer immunotherapy by immunosuppression

We have previously suggested that the stimulatory effect of a weak immune reaction on tumor growth may be necessary for the growth of incipient tumors. In the present paper, we enlarge upon and extend that idea by collecting evidence in the literature bearing upon this new hypothesis that a growing cancer, whether in man or mouse, is throughout its lifespan, probably growing and progressing because of continued immune stimulation by a weak immune reaction. We also suggest that prolonged immunosuppression might interfere with progression and thus be an aid to therapy. While most of the considerable evidence that supports the hypothesis comes from observations of experimental mouse tumors, there is suggestive evidence that human tumors may behave in much the same way, and as far as we can ascertain, there is no present evidence that necessarily refutes the hypothesis

Immunologgical self-tolerance in allophenic and embryo-aggregated mice

<p>Abstract</p> <p>Allophenic mice, supposedly containing almost equal numbers of cells derived from embryos of mouse strains C57Bl and FVB, were shown in a recent paper to grow the B16 melanoma, a long transplanted tumor of C57Bl origin, much better than did mice of either the parental C57Bl strain or the C57Bl × FVB F1 hybrid. Mice containing smaller proportions of C57Bl cells rejected the tumor. A reconsideration of these suprising data, in light of the current literature, suggests that the better growth of the tumor in the 50-50% allophenics than in the C57Bl parental strain was almost certainly caused by the tumor stimulation engendered by a weak anti-C57Bl immune reaction in the overtly healthy allophenic mice.</p