Surveillance, latency and the two levels of MCA‐induced tumor immunogenicity

Abstract

Among 154 different, MCA-induced mouse sarcomas, the immunogenicities of those tumors that had had the shortest original latencies in their autochthonous hosts were of an intermediate level with relatively little scatter. This fact is not predicted by the theory of immunological surveillance, but does fit the predictions of the immunological facilitation theory of oncogenesis. The frequency distribution of the tumor immunogenicities showed 2 peaks; the cluster of higher immunogenicity had a shorter latency than did the cluster of lower immunogenicity. The data for tumors initiated within in vivo diffusion chambers also showed 2 immunogenicity clusters, suggesting that the discrete clusters were not caused by host immunity. However, immunity apparently reduced the mean latency of the more immunogenic cluster and/or lengthened the mean latency of the less immunogenic, a result also inconsistent with the theory of immunological surveillance.

Long-lived and transferable tumor immunity in mice after targeted interleukin-2 therapy.

“…Studies of Prehn et al have convincingly illustrated that the majority of murine tumors are immunogenic, as revealed by vaccination with irradiated tumor cells or by surgical excision of a growing tumor mass (15,16). This inherent immunogenicity markedly complicates the assessment of the immunostimulatory properties of therapeutic manipulations.…”

On the nature of cancer and why anticancer vaccines don't work

“…The little immune response these tumors might engender would be expected, judging by these Winn test results, to stimulate rather than inhibit tumor growth. This was emphatically confirmed in a variety of extensive studies which showed, among other things, that a newly induced in situ mouse tumor, mesenchymal or epithelial, was stimulated to grow faster (had a shorter latency) if it could engender an immune response [8,11]. Even tumors that subsequently were shown to be highly immunogenic usually grew faster than tumors of little or no immunogenicity when the tumors were left undisturbed in their primary hosts [11].…”

“…Thus, chemical oncogenesis is not obviously altered by immunodepression [7]; the tumor immunogenicity and/or the degree of immune depression must be very carefully titrated in order to see any effect of immune depression, either positive or negative [8,9]. Both within and without the immunologically isolated environment of intraperitoneal diffusion chambers, nonimmunogenic tumors are commonly induced [10,11]. Furthermore, chemically-induced tumorigenesis may actually be lessened, not increased, in immunologically crippled, germ-free nude mice as compared with their essentially normal heterozygous nude controls [8].…”

Cancer may be caused by the Immune Reaction

“…These differences were highly significant and ancillary data suggested that they were indeed caused by differences in the strengths of the immune reactions [30] . One would have expected, according to the surveillance hypothesis, that tumors of the least average immunogenicity would have had the shortest, rather than the longest, average latency.…”

“…Further data demonstrating the relative tumorenhancing action of low-dose immunity, relative to the effect of either lower or higher dosages, was found in the relationship between the latencies of tumors and their immunogenicities. Among 154 sarcomas induced in mice by a constant dosage of MCA, it was observed that the tumors of shortest latencies had intermediate levels of immunogenicity [30] . Thus, the first 34 tumors to arise (latency of 8-12 wks) had an average immunogenicity (growth advantage of tumor implants in control versus growth in immunized recipients) of 2.84, the next 38 (latency of 13-15wks) had an increased average immunogenicity of 4.48, while tumors with only1.5 to non detectable levels of immunogenicity had an average latency in excess of 19wks.…”